How Do Stem Cells Respond To Diagnostic Radiation Studies?

MedicalResearch.com Interview with:
http://www.insilico.com/
Andreyan Osipov PhD
Insilico Medicine and
Dmitry Klokov PhD
Canadian Nuclear Laboratories, Chalk River, Ontario, Canada 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cells and tissues can be damaged when exposed to ionizing radiation. In case of radiotherapy, it is a desirable effect in tumor cells. In case of occupational, medical and accidental exposures, typically to low-dose radiation, this may pose health risk to normal cells and tissues.

In both cases, short-term assays that quantify damage to DNA and help evaluate long-term outcome are key to treatment/risk management. One such short-term assay is based on quantification of a modified histone protein called gH2AX in exposed cells up to 24 hrs after exposure. This protein marks sites in DNA that have both strands of the DNA helix broken or damaged. This assay is also widely used for various applications, including determination of individual radiosensitivity, tumor response to radiotherapy and biological dosimetry. With the advent of regenerative medicine that is based on stem cell transplantation, the medical and research communities realized that there is a need to understand how stem cells respond to low-dose diagnostic radiation exposures, such as CT scans. Stem cell therapies may have to be combined with diagnostic imaging in recipient patients. The gH2AX assay comes in very handy here, or at least it seemed this way.

We exposed mesenchymal stem cells isolated from human patients to low or intermediate doses of X-rays (80 and 1000 mGy) and followed formation of gH2AX in their nuclei. First we found that residual gH2AX signal in cells exposed to a low dose was higher than in control non-irradiated cells. If the conventional assumptions about this assay that it is a surrogate for long-term detrimental effects was followed it would mean that the low-dose exposed cells were at a high risk of losing their functional properties. So we continued growing these cells for several weeks and assayed gH2AX levels, ability to proliferate and the level of cellular aging. Surprisingly, we found that low-dose irradiated cells did not differ from non-irradiated cells in any of the measured functional end-points. This was in contrast to 1000 mGy irradiated cells that did much worse at those long-term end points.

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Testicular Cancer Stem Cells Highly Sensitive To Chemotherapy, Resulting In High Cure Rates

MedicalResearch.com Interview with:

 Credit: Tim Pierpont, Cornell University

A low magnification image of a germ cell tumor, called a teratocarcinoma, from a new mouse model developed to study testicular cancer. A cluster of cancer stem cells, termed embryonal carcinoma, is shown at higher magnification at the bottom.

 

Amy M. Lyndaker, Ph.D.
Assistant Professor of Biology
Division of Mathematics and Natural Sciences
Elmira College
This work was completed when I was a Research Associate in the laboratory of
Dr. Robert S. Weiss at:
Department of Biomedical Sciences College of Veterinary Medicine
Cornell University Ithaca, NY

 

 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There has been this puzzle in the field of cancer biology that testicular cancers, even after they have spread to the brain or the lungs, are often able to be cured with radiation and chemotherapy (think of Lance Armstrong, for instance), whereas the majority of cancers are not curable with similar treatments. We thought that this could be due to the unique properties of the cells from which the cancers are derived; testicular cancers arise from germ cells (which later go on to make sperm), whereas most cancers arise from somatic cells (body cells). We proposed that maybe the germ cells and somatic cells were hard-wired to respond differently to DNA damage, and that because of this, cancers derived from these two distinct types of cells might then respond differently to chemotherapies (which typically kill cancer cells by creating DNA damage).

To test this, we generated a novel genetic mouse model that develops cancers similar to the malignant testicular cancers seen in young men. We then used standard chemotherapies (cisplatin alone, or combined bleomycin/etoposide/cisplatin), and found that treatment with DNA-damaging chemotherapies specifically killed the cancer stem cells within the tumors. Thus, we were able to show that testicular cancers are curable with standard DNA-damaging chemotherapies because their stem cells are highly sensitive to DNA damage. This is in contrast to most cancers, where the cancer stem cells are refractory to treatment and are responsible for tumor recurrence and metastasis.

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American CryoStem – CRYO – Allows Individuals to Collect, Freeze and Store Their Stem Cells

MedicalResearch.com Interview with:

John Arnone, Chairman and CEO American CryoStem Corporation

John Arnone

John Arnone
Chairman and CEO

American CryoStem Corporation

MedicalResearch.com: What is the background for this your company American CryoStem?

Response: American CryoStem Corporation (CRYO) was founded in 2008, to allow individuals, researchers and physicians to collect-process-store stem cells derived from adipose tissue (fat) to prepare for their current or future use. Over the years the Company has become a biotechnology pioneer, standardizing adipose tissue derived technologies (Adult Stem Cells) for the fields of Regenerative and Personalized Medicine.

The Company operates a state-of-art, FDA-registered, clinical laboratory in New Jersey and licensed laboratories in Hong Kong, China and Tokyo, Japan, which operate on our proprietary platform, dedicated to the collection, processing, bio-banking, culturing and differentiation of adipose tissue (fat) and adipose derived stem cells (ADSCs)

CRYO maintains a strategic portfolio of intellectual property, 18 patents that surround the Companies proprietary technology which supports a growing pipeline of stem cell applications and biologic products. We are leveraging our proprietary platform and our developed product portfolio to create a domestic and global footprint of licensed laboratory affiliates, physicians networks and research organizations who purchase tissue collection, processing and storage services and consumables from the Company.

CRYO’s laboratory stem cell bank/line products are characterized adult human Mesenchymal Stem Cell (MSC’s) derived from adipose tissue that work in conjunction with our 13 patented (non-animal) medium lines.

The Company’s R&D efforts are focused on university and private collaborations to discover, develop and commercialize ADSC therapies by utilizing our standardized collection-processing-storage methodology and laboratory products combined with synergistic technologies to create jointly developed regenerative medicine applications and intellectual property.

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Skin-Grafted Stem Cells May Treat Obesity and Diabetes

MedicalResearch.com Interview with:

Dr. Xiaoyang Wu PhD Ben May Department for Cancer Research The University of Chicago, Chicago, IL

Dr. Xiaoyang Wu

Dr. Xiaoyang Wu PhD
Ben May Department for Cancer Research
The University of Chicago, Chicago, IL

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have been working on skin somatic stem cells for many years. As one of the most studies adult stem cell systems, skin stem cells have several unique advantages as the novel vehicle for somatic gene therapy (summarized also in the paper). The system is well established. Human skin transplantation using CEA device developed from skin stem cells have been clinically used for decades for burn wound treatment, and been proven to be safe the effective.

In this study, we developed a skin 3D organoid culture model to induce stratification and maturation of mouse epidermal stem cells in vitro, which allows us to efficiently transfer engineered mouse skin to isogenic host animals. In the proof of concept study, we showed that we can achieve systematic release of GLP1 at therapeutic concentration by engineered skin grafts.

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Preclinical Study Finds Cancer Stem Cell Inhibitor Sensitizes Colon Cancer Cells To Immunotherapy

MedicalResearch.com Interview with:
Dr. Yuan Gao

Assistant Investigator at Boston Biomedical

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Colorectal cancer (CRC) is the third most commonly diagnosed malignant disease and third most frequent cause of cancer-related death in the United States. Standard treatment for unresectable metastatic CRC currently includes first and second line 5-fluorouracil (5-FU)-based chemotherapy regimens. However, CRC patients often develop chemoresistance. Recently, immunotherapy has emerged as a revolutionary new treatment for CRC. However, with the exception of a small percentage of CRC patients that display microsatellite instability (MSI), the vast majority of colorectal cancer patients have been found to be resistant to immune checkpoint therapies.

Cancer stem cells (CSCs), a highly malignant tumor cell subpopulation capable of self-renewal, are considered to be fundamentally responsible for malignant growth and tumor recurrence. Emerging evidence indicates that CSCs and cancer stemness pathways, such as STAT3, beta-Catenin, CD44 and Nanog, are involved in the immune evasion of cancers. BBI-608 (napabucasin) is an orally-administered first-in-class cancer stemness inhibitor that works by targeting STAT3. In this study, we investigated the effect of cancer stemness inhibition on sensitizing colorectal cancer to immune checkpoint inhibitors in preclinical models.

In the syngeneic microsatellite stable (MSS) tumor model, CT26, an anti-PD-1 antibody delivered as a monotherapy, produced low level and temporary antitumor activity with rapid development of complete resistance to anti-PD-1 treatment. The anti-PD-1 antibody-treated CT26 tumors exhibited increased p-STAT3 activation and overexpression of a variety of stemness factors, as well as enrichment of sphere-forming stemness-high cancer cells. Napabucasin was able to reduce basal as well as anti-PD1-induced STAT3 activation and other CSC features within CT26 tumors. The combination of a stemness inhibitor – napabucasin – with the anti-PD-1 antibody led to tumor complete response (CR) in all treated CT26 tumors, with 40 percent of the mice remaining tumor-free for 30 days following treatment termination. This combination also had a synergistic effect on the influx of tumor infiltrating CD8+ T cells, which likely contributed to the rapid tumor regression. Finally, mice CR-induced by napabucasin and the anti-PD-1 antibody were able to reject CT26 tumors upon re-challenge, but not the unrelated breast cancer 4T1 tumors.

MedicalResearch.com: What should readers take away from your report?

Response: Our data suggest cancer stemness pathways contribute to immunotherapy resistance in MSS CRC, a subtype representing the vast majority of colorectal cancer cases. Furthermore, inhibition of cancer stemness by BBI-608 sensitizes colorectal cancer to immune checkpoint inhibition, producing striking regression in a large proportion of the tumors treated.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study provides compelling preclinical evidence to support the investigation of the combination of napabucasin with immune checkpoint inhibitors in CRC. While this study specifically investigated the combination with anti-PD-1, the combination with other immunotherapies could be studied as well.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: AACR 2017 Abstract

Inhibition of cancer stemness sensitizes colorectal cancer to immune checkpoint inhibitors
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Human Stem Cells Can Be Used For 3-D Printing of Tissue Stuctures

MedicalResearch.com Interview with:

Sang Jin Lee, Ph.D. Associate Professor of Wake Forest Institute for Regenerative Medicine Wake Forest School of Medicine Wake Forest University

Dr. Sang Jin Lee

Sang Jin Lee, Ph.D.
Associate Professor of Wake Forest Institute for Regenerative Medicine
Wake Forest School of Medicine
Wake Forest University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: I received my Ph.D. in Chemical Engineering at Hanyang University, Seoul, South Korea in 2003 and took a postdoctoral fellowship in the Laboratories for Tissue Engineering and Cellular Therapeutics at Harvard Medical School and Children’s Hospital Boston and the Wake Forest Institute for Regenerative Medicine where I am currently a faculty member. My research works have focused on development of smart biomaterial systems that support the regenerative medicine strategies and approaches. These biomaterial systems combined with drug/protein delivery system, nano/micro-scaled topographical feature, or hybrid materials that could actively participate in functional tissue regeneration. Recently my research works utilize 3D bioprinting strategy to manufacture complex, multi-cellular living tissue constructs that mimic the structure of native tissues. This can be accomplished by optimizing the formulation of biomaterials to serve as the scaffolding for 3D bioprinting, and by providing the biological environment needed for the successful delivery of cells and biomaterials to discrete locations within the 3D structure.

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RepliCel Developing Autologous Cell Therapies For Skin, Hair and Tendon Regeneration

MedicalResearch.com with:

Lee Buckler, CEO
RepliCel Life Sciences

MedicalResearch.com: What is the background for this your company, RepliCel.com?

Response: RepliCel Life Sciences is a Canadian regenerative medicine company based in Vancouver, British Columbia that was founded in 2006. The company focuses on the development of cell therapies using a patient’s own cells (autologous cell therapy). It is developing treatments targeted at healing chronic tendon injuries that have failed to heal properly, hair restoration, and the treatment of damaged and aged skin.

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Process Refines Conversion of Skin Fibroblasts into Cardiac Blood Vessels

MedicalResearch.com Interview with:

Jalees Rehman, MD Director of Research, Division of Cardiology Associate Professor of Medicine and Pharmacology University of Illinois at Chicago College of Medicine Chicago, IL 60612

Dr. Rehman

Jalees Rehman, MD
Director of Research, Division of Cardiology
Associate Professor of Medicine and Pharmacology
University of Illinois at Chicago
College of Medicine
Chicago, IL 60612

MedicalResearch.com: What is the background for this study?

Response: Converting skin fibroblasts into regenerative blood vessel endothelial cells could be a valuable approach to repair diseased blood vessels in patients with cardiovascular disease and also to build new blood vessels in order to supply engineered tissues and organs.

Using skin fibroblasts is very well suited for personalized therapies because they can be obtained from a skin biopsy in an outpatient setting. The biopsied skin sample is used to extract the skin fibroblasts, which are then expanded in cell culture dishes before they are converted to endothelial cells. This allows for the generation of tens or hundreds of millions of cells that will likely be needed for blood vessel repair and regeneration. By converting skin fibroblasts of a patient, we can generate personalized endothelial cells with the same genetic signature as the patient so that they are less likely to be rejected if implanted back into the same patient after the conversion.

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Nasal Spray of Stem Cell Vesicles First Step Toward Treating Brain Diseases

MedicalResearch.com Interview with:

Dr. Darwin J. Prockop, M.D., Ph.D. Professor and Director Institute for Regenerative Medicine Texas A&M Health Science Center College of Medicine Temple, TX

Dr. Prockop

Dr. Darwin J. Prockop, M.D., Ph.D.
Professor and Director
Institute for Regenerative Medicine
Texas A&M Health Science Center College of Medicine
Temple, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We and many others have been trying for many years to develop therapies with adult stem cells that might rescue the brain from the injuries and disease. Recently many of found that small vesicles secreted by adult stem cells have many of the beneficial effects of the cells themselves. The paper shows that a nasal spray of the vesicles can rescue mice from the long-term effects of severe epilepsy.

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Transplanted Human Embryonic Stem Retinal Pigment Cells Survive 22 months in a Human Recipient

MedicalResearch.com Interview with:

Won Kyung Song MD.PhD Assistant Professor, Vitreoretinal service, Department of Ophthalmology CHA Bundang Medical Center CHA University Republic of Korea

Dr. Won Kyung Song

Won Kyung Song MD.PhD
Assistant Professor, Vitreoretinal service, Department of Ophthalmology
CHA Bundang Medical Center CHA University
Republic of Korea 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The retina is a light-sensitive neural tissue lining the inner surface of the human eye. The center of this retina is called the “macula”, which is responsible for high quality vision and central visual field. Retinal pigment epithelium is a layer of cells in the outer layer of the retina which has a critical role in maintaining and supporting the retina, especially the macula.

Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly in Western countries. There are two types of AMD, wet (neovascular or exudative) and dry (atrophic). The retinal pigment epithelium and choroid, are closely related with the pathophysiology of AMD. In dry AMD, age-related degeneration of RPE cells leads to the loss of photoreceptor cells and visual deficit. Currently, some therapies are available for ameliorating the wet AMD. However, there are no effective therapy available for dry AMD.

Previous studies have shown that healthy RPE cells can be implanted to replace unhealthy RPE cells in lesion areas where RPE cells have been lost. Allogenic RPEs resulted in graft rejection and autologous RPEs are difficult to harvest leading to surgery related complications. Now, abundant RPEs with stable genotype and phenotye may be generated from embryonic stem cells. Therefore, we have undergone subretinal transplantation of human embryonic stem cell derived RPE cells. (Clinicaltrials.gov NCT 01674829) Among the patients enrolled for

this clinical trial, we noted epiretinal membrane(ERM) with pigmentations over the retina in a proportion of patients as an adverse event. One patient with dry AMD and an epiretinal membrane after the hES-RPE transplantation undergone removal of this ERM. The histologic examination of this ERM with pigmentations showed that the pigmented cells originated from the transplanted hES-RPE cells which survived in the recipient for 22 months without anaplasia.

MedicalResearch.com: What should readers take away from your report?

Response: The main concerns of clinical application of hES derived cells are tumorigenesis and immune rejection.

There are limitations of these trials lacking confirmative measurements of engraftment of the transplanted cells. Because biopsy of the retina results in focal loss of nurosensory retina and labelling the cells may cause additional clinical harm.

This is the first report showing that hES derived cells has survived upto 22 months in human organ without anaplasia and may form an ERM.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Objective measurement of engraftment is necessary, together with advancement of an objective visual function measurements.

MedicalResearch.com: Is there anything else you would like to add?

Response: The case reported in this journal is a finding from a patient enrolled in the clinical trial sponsored by CHAbiotech.Co,Ltd.

HI12C1794(A121941)

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Shim SH, Kim G, Lee DR, Lee JE, Kwon HJ, Song WK. Survival of Transplanted Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells in a Human Recipient for 22 Months. JAMA Ophthalmol. Published online February 09, 2017. doi:10.1001/jamaophthalmol.2016.5824

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Smaller and More Stable Than Stem Cells, Exosomes Can Preserve Retinal Cell Function

MedicalResearch.com Interview with:

Ben Mead, BSc, MRes, PhD Section of Retinal Ganglion Cell Biology Laboratory of Retinal Cell and Molecular Biology National Eye Institute, National Institutes of Health Bethesda, Maryland 20892

Dr. Ben Mead

Ben Mead, BSc, MRes, PhD
Section of Retinal Ganglion Cell Biology
Laboratory of Retinal Cell and Molecular Biology
National Eye Institute, National Institutes of Health
Bethesda, Maryland 20892

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Retinal ganglion cells (RGC) in the back of the eye transmit visual information to the brain, via long thread-like extensions called axons, which make up the optic nerve. Loss of these cells is the leading cause of irreversible blindness and can occur through trauma or degenerative diseases, such as glaucoma or optic neuritis. While no treatment yet exists to directly protect RGC from death, mesenchymal stem cells, a type of stem cell isolated from adult bone marrow, have shown therapeutic efficacy in various animal models and are currently undergoing clinical trials.

In this study, we aimed to isolate exosomes, which are small, membrane-enclosed vesicles secreted by bone marrow stem cells (BMSC) and that we believe are associated with the therapeutic effect of BMSCs. Injecting these exosomes into the eyes of animals following an optic nerve injury, was associated with significant neuroprotection of RGC, as well as preservation of RGC function. The protective effects of exosomes appeared to be through their delivery of microRNA, molecules that interfere with or silence gene expression.

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Reduced Stem Cells Link Congenital Heart Disease To Impaired Brain Growth

MedicalResearch.com Interview with:

Childrens National Research Team

Children’s National Research Team

Paul D. Morton, Ph.D.
Research PostDoc and lead study author of “Abnormal Neurogenesis and Cortical Growth in Congenital Heart Disease.”
Children’s National Health System Washington, DC

Nobuyuki Ishibashi, M.D.
Director of the Cardiac Surgery Research Laboratory at Children’s National Health System and co-senior study author.

Vittorio Gallo, Ph.D.
Director of the Center for Neuroscience Research at Children’s National Health System and co-senior study author.

 

 

Richard A. Jonas, M.D.
Chief of the Division of Cardiac Surgery at Children’s National Health System and co-senior study author.

MedicalResearch.com: What is the background for this study?

Response: Congenital heart disease (CHD) is the leading birth defect in the United States and often results in an array of long-term neurological deficits including motor, cognitive and behavioral abnormalities. It has become increasingly clear that children with CHD often have underdeveloped brains. In many cases of complex CHD, blood flow to the brain is both reduced and less oxygenated, which has been associated with developmental abnormalities and delay. The cellular mechanisms underlying the impact of CHD on brain development remain largely unknown. We developed a preclinical chronic hypoxia model to define these mechanisms.

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Healthy Stem Cells Need Just Right Telomere Length

MedicalResearch.com Interview with:

Professor Jan Karlseder Molecular and Cell Biology Laboratory Donald and Darlene Shiley Chair Salk Institute for Biological Studies

Prof. Jan Karlseder

Professor Jan Karlseder
Molecular and Cell Biology Laboratory
Donald and Darlene Shiley Chair
Salk Institute for Biological Studies

MedicalResearch.com: What is the background for this study? 

Response: Telomeres are repetitive stretches of DNA at the ends of each chromosome whose length can be increased by an enzyme called telomerase. Our cellular machinery results in a little bit of the telomere becoming lopped off each time cells replicate their DNA and divide. As telomeres shorten over time, the chromosomes themselves become vulnerable to damage. Eventually the cells die. The exception is stem cells, which use telomerase to rebuild their telomeres, allowing them to retain their ability to divide, and to develop (“differentiate”) into virtually any cell type for the specific tissue or organ, be it skin, heart, liver or muscle—a quality known as pluripotency. These qualities make stem cells promising tools for regenerative therapies to combat age-related cellular damage and disease.

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Kidney Organoids Derived from Human Pluripotent Stem Cells Model Polycystic Disease

MedicalResearch.com Interview with:

Ryuji Morizane M.D. Ph.D. Associate Biologist, Renal Division, Brigham and Women’s Hospital Affiliated Faculty, Harvard Stem Cell Institute Instructor, Harvard Medical School

Dr. Ryuji Morizane

Dr. Ryuji Morizane MD, PhD
Associate Biologist, Renal Division
Brigham and Women’s Hospital
Affiliated Faculty, Harvard Stem Cell Institute
Instructor, Harvard Medical School

MedicalResearch.com: What is the background for this study?

Response: Polycystic kidney disease (PKD) accounts for 10% of end-stage kidney disease (ESKD), and there is currently no curable treatment available for patients with PKD.

The adult onset form of PKD, the most common type of PKD, takes 30 years to form cysts in humans; therefore, it is difficult to study mechanisms of PKD to find novel therapeutics for patients.

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Breast Cancer Cells Become Chemotherapy Resistant By Eating Surrounding Stem Cells

MedicalResearch.com Interview with:

Thomas Bartosh Jr, Ph.D. Assistant Professor Medical Physiology Texas A&M Health Science Center

Dr. Thomas Bartosh Jr,

Thomas Bartosh Jr, Ph.D.
Assistant Professor Medical Physiology
Texas A&M Health Science Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: One mysterious and devastating aspect of breast cancer is that it can reemerge abruptly, often as metastatic disease, in patients many years after an apparent eradication of the primary tumor. The sudden reappearance of cancer has been termed relapse and is thought to occur because a minimal number of resilient tumor cells are able to evade frontline therapies and linger in an undetectable/dormant state somewhere in the body for an unpredictable amount of time. Then, for reasons that remain unclear, these same dormant cells awaken and rapidly grow, and produce almost invariably fatal cancerous lesions. The therapeutic challenges of tumor dormancy and need to decode the underlying mechanisms involved are apparent.

Cancer cell behavior is strongly influenced by various non-malignant cell types that are found within the tumor mass itself and that help make up the tumor microenvironment (TME). In particular, bone marrow-derived mesenchymal stem/stromal cells (MSCs), which are actively recruited into the tumor stroma, directly interact with carcinoma cells and significantly impact cancer progression, although the role of MSCs in tumor dormancy remains ill-defined.

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Switch Stimulating New Insulin-Producing Cells Could Lead To Cure For Type I Diabetes

MedicalResearch.com Interview with:

Dr. Fred Levine MD PhD Professor & Director Sanford Children's Health Research Center Sanford Burnham Prebys Medical Discovery Institute La Jolla, CA

Dr. Fred Levine

Dr. Fred Levine MD PhD
Professor & Director
Sanford Children’s Health Research Center
Sanford Burnham Prebys Medical Discovery Institute
La Jolla, CA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study is the latest in a series that began in 2010 when we published that the combination of severe pancreatitis and ablation of preexisting pancreatic beta-cells led to the formation of new beta-cells by direct conversion of alpha-cells, which are the neighboring cells in the islets of Langerhans producing glucagon, which like insulin is also involved in glucose homeostasis.

The phenomenon of generating new beta-cells by islet cell transdifferentiation went against the conventional wisdom in the field, which is that most beta-cell neogenesis in adults occurs by differentiation from cells in the pancreatic ducts, similar to what happens during embryogenesis. Since then, we have shown that beta-cell neogenesis by islet cell transdifferentiation appears to occur in murine and human type I diabetes, making it highly translationally relevant.

Understanding the mechanism by which new beta-cells are formed from alpha-cells is required for eventual clinical translation. The current study describes that mechanism, which involves the activation of an atypical G protein coupled receptor called Protease Activated Receptor 2 (PAR2). Unlike most other GPCRs, it is activated by extracellular proteases such as are found in the exocrine pancreas or following tissue damage. PAR2 activation by an injectable peptide agonist was both necessary and sufficient to induce beta-cell neogenesis when preexisting beta-cells are absent, as occurs in type I diabetes.

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Stem Cells From Nose Used To Repair Knee Cartilage

MedicalResearch.com Interview with:

Professor Ivan Martin, PhD Department of Surgery and Department of Biomedicine University Hospital Basel University of Basel, Basel, Switzerland

Prof. Ivan Martin

Professor Ivan Martin, PhD
Department of Surgery and Department of Biomedicine
University Hospital Basel
University of Basel
Basel, Switzerland

MedicalResearch.com: What is the background for this study and new use of autologous nasal chondrocytes?

Response: We previously demonstrated that nasal chondrocytes, harvested from the nasal septum, have a larger and more reproducible capacity to form new cartilage than articular chondrocytes, harvested from the knee joint. We further established that the cartilage tissue generated by nasal chondrocytes can respond to physical forces (mechanical loads) similar to articular cartilage and has the ‘plasticity’ to adapt to a joint environment, since it efficiently integrated with surrounding articular cartilage when implanted in goat joints. This was the rationale for using nasal chondrocytes for articular cartilage repair.

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Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers

MedicalResearch.com Interview with:

Lukasz Antoniewicz MD PhD candidate Karolinska Institutet Department of Clinical Sciences Danderyd University Hospital Stockholm, Sweden

Dr. Lukasz Antoniewicz

Lukasz Antoniewicz MD, PhD candidate
Karolinska Institutet
Department of Clinical Sciences
Danderyd University Hospital
Stockholm, Sweden

MedicalResearch.com: What is the background for this study?

Response: Electronic cigarette sales increase exponentially on a global scale without knowledge about possible negative effects on human health. We performed an exposure study in young healthy volunteers and analyzed blood samples for endothelial progenitor cells and microvesicles. Increase in those markers may reflect vascular injury, inflammation and platelet activation.

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Stem Cells Drive Vascular Calcification in Arteriosclerosis

MedicalResearch.com Interview with:
Rafael Kramann, MD, FASN
RWTH Aachen University
Division of Nephrology and Clinical Immunology
Pauwelsstr 30
52074 Aachen, Germany

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vascular calcification contributes centrally to the increased cardiovascular morbidity and mortality in patients with diabetes or chronic kidney disease.

Vascular calcification is of major clinical importance as it predicts cardiovascular events, affects plaque stability contributing to stroke and myocardial infarction and also contributes to chronic heart failure by stiffening of the arterial wall. However, the cellular origin of vascular calcification is incompletely understood. While it is known that resident vascular smooth muscle cells and circulating macrophages are involved the contribution of adventitial cells is controversial and partly unknown.

Our data indicates that adventitial progenitor cells marked by expression of Gli1 are key drivers of vascular calcification in athero- and arteriosclerosis. Genetic ablation of this cell population completely abolished vascular calcification in a mouse model of high lipid load and chronic kidney disease. Identification of this progenitor population might be the first step towards a cell-specific targeted therapy of vascular calcification.

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Cord Blood Transplant in Leukemia With Minimal Residual Disease

MedicalResearch.com Interview with:

Dr. Filippo Milano, MD, PhD Assistant Member, Clinical Research Division Associate Director Cord Blood Transplantation Cord Blood Program Assistant Professor, University of Washington Fred Hutchinson Cancer Research Center

Dr. Filippo Milano

Dr. Filippo Milano, MD, PhD
Assistant Member, Clinical Research Division
Associate Director Cord Blood Transplantation
Cord Blood Program
Assistant Professor, University of Washington
Fred Hutchinson Cancer Research Center

MedicalResearch.com: What is the background for this study?

Response: When first introduced, cord blood (CB) graft was used only as a last resort when no suitable conventional donor could be identified, largely due to the limiting cell doses available in a cord blood graft. A CB graft, however, is attractive due to the increased level of HLA disparity that can be tolerated, without increased risk of graft versus host disease, allowing nearly all patients to find such a donor.

The main intent of the study was to evaluate whether or not, at our Institution, cord blood SHOULD STILL BE considered only AS an alternative DONOR or IF instead outcomes were comparable to those obtained with more “conventional” types of transplants from matched and mismatched unrelated donors.

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Stem Cells May Be Stimulated in Women With Chest Pain But Normal Coronary Arteries

MedicalResearch.com Interview with: Arshed A. Quyyumi MD; FRCP

Dr. Arshed Auyyumi

MedicalResearch.com Interview with:
Arshed A. Quyyumi MD; FRCP
Professor of Medicine, Division of Cardiology
Emory University School of Medicine
Co-Director, Emory Clinical Cardiovascular Research Institute
Atlanta GA 30322

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Circulating progenitor or stem cells were discovered in adults 15 years ago. We now know that they may be stimulated by injury or ischemia, and they go down in number and function with aging, particularly when aging is associated with risk factors.

Women with chest pain despite normal coronary arteries are thought to have ischemia because of microvascular dysfunction. We found that these women, with the worst microvascular function (measured as coronary flow reserve), had higher levels of circulating stem or progenitor cells. This implies that the mild ischemia they are having during their normal daily life, leads to stimulation of their stem cells. Also, the vascular abnormality may be a stimulus for repair.

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Cardioprotective Effect of Metformin in Diabetes Determined

MedicalResearch.com Interview with:

Jolanta U Weaver, FRCP MRCS PhD CTLHE

Dr. Jolanta Weaver

Jolanta U Weaver, FRCP MRCS PhD CTLHE
Senior Lecturer in Diabetes Medicine
Honorary Consultant Diabetologist
Newcastle

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vascular stem cells, which are associated with an improvement of heart disease, are improved in type 1 diabetes by repurposing metformin, known to reduce heart disease in type 2 diabetes.

We treated patients with type 1 diabetes with metformin for 8 weeks. The metformin dose varied between 500 mg a day to 2000 mg a day, depending on what patients were happy to take. Subjects were requested to keep diabetic control unchanged to study the direct effect of metformin on heart disease. Circulating endothelial progenitor cells (vascular stem cells) count, Hill’s colonies and pro angiogenic cells function (in test tube) improved in comparison to patients, who did not take metformin but remained on standard therapy.

Endothelial cells associated with vascular damage, on the other hand, were reduced following metformin therapy confirming improved vascular health. The glycaemic control remained unchanged (as planned at the onset of the study) to allow us to examine the effect of metformin ALONE on vascular health. Patients did not suffer any serious side effects.

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IV Administration of Stem Cells Viable and More Practical Than Direct Cardiac Implantation

MedicalResearch.com Interview with:

Javed Butler, M.D., MPH, FACC, FAHA Chief of the Cardiology Division and Co-Director of the Heart Institute at Stony Brook University Stony Brook Heart Institute

Dr. Javed Butler

Javed Butler, M.D., MPH, FACC, FAHA
Chief of the Cardiology Division and Co-Director of the Heart Institute at Stony Brook University
Stony Brook Heart Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It was previously assumed that stem cells must be delivered directly to the myocardium to improve patient outcomes. However, this delivery mechanism – either in the coronary artery or the myocardium – may not be feasible for millions of patients and for repeat injections. This study represents the first clinical trial to observe the effects of intravenous (IV) administration of ischemia-tolerant mesenchymal stem cells (itMSCs) in patients with chronic heart failure. Results show that an IV injection strategy is safe and well-tolerated.In addition, the data illustrate statistically significant improvement in 6-minute walk test, quality-of-life scores as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) and favorable immune modulatory benefits.

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SkinGun™ Sprays Patient’s Own Stem Cells Onto Burns or Wounds To Accelerate Healing

MedicalResearch.com Interview with:

Thomas Bold President and CEO Communications at TrendLogic RenovaCare Inc.

Thomas Bold

Thomas Bold
President and CEO
RenovaCare Inc.

MedicalResearch.com: What is the background for the CellMist™ System? How are the stem cells harvested and processed?

Response: Our flagship CellMist™ System makes use of a patient’s own stem cells, which are sprayed onto wounds using our novel SkinGun™ device.

For patients suffering severe burns and other wounds, the prospect of a quick-healing, gentle spray containing their own stem cells will be a promising alternative to conventional skin graft surgery, which can be painful, prone to complications like infections, and slow-to-heal.

Based on preliminary case studies, CellMist™ System patients can be treated within 90 minutes of arriving in an emergency room; a patient’s stem cells are isolated, processed, and sprayed on to the wound sites for rapid healing.

The CellMist™ Solution is a liquid suspension containing a patient’s own regenerative skin stem cells. A small sample (as small as a square inch) of the patient’s skin is quickly processed to liberate the stem cells from surrounding tissue. The resulting product is referred to as the ‘CellMist™ Solution’. The CellMist™ Solution is placed in the SkinGun™ and gently sprayed onto the patient’s wound.

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Stem Cells, Not Their Progeny, Found Competent To Initiate Basal Cell Skin Cancer Formation

MedicalResearch.com Interview with:

Cédric Blanpain, MD, PhD Professor of Stem Cell and Developmental Biology WELBIO, Interdisciplinary Research Institute (IRIBHM) Université Libre de Bruxelles (ULB) Belgium

Dr. Cédric Blanpain

Cédric Blanpain, MD, PhD
Professor of Stem Cell and Developmental Biology
WELBIO, Interdisciplinary Research Institute (IRIBHM)
Université Libre de Bruxelles (ULB)
Belgium
MedicalResearch.com: What is the background for this study?

Response: Many cancers arise from tissues maintained by stem and progenitor cells that ultimately give rise to non-dividing terminally differentiated cells. However, little is known about the contribution of stem cells and progenitors to cancer initiation. During tumor initiation, cells targeted by oncogenic mutations undergo a series of molecular changes leading to their clonal expansion and the acquisition of invasive properties. How exactly oncogenic mutations impact on the rate of stem cell and progenitor division, and change the proportion of divisions that result in symmetric and asymmetric cell fate, allowing clonal expansion and tumor progression is poorly understood. In this new study, we define for the first time the clonal dynamics that lead to skin cancer initiation using the basal cell carcinoma, the most frequent tumor in humans, as a model.

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Small Study Demonstrates Benefit of Stem Cell Transplantation in Hearts ‘Broken’ By STEMI

MedicalResearch.com Interview with:

Fu Guosheng MD Professor and Chairman, Department of Cardiology Sir Run Run Shaw Hospital, College of Medicine Zhejiang University Hangzhou, China

Dr. Fu Guosheng

Fu Guosheng MD
Professor and Chairman, Department of Cardiology
Sir Run Run Shaw Hospital, College of Medicine
Zhejiang University
Hangzhou, China

MedicalResearch.com: What is the background for this study?

Response: Acute myocardial infarction (AMI) remains a major cause of long term morbidity and mortality worldwide. Although we can re-vascularize the occluded vessels by cardiac intervention or coronary artery bypass graft (CABG), it is not helpful for the damaged myocardium, which urges us to find a new therapeutic method. An increasing body of evidence from a wide range of experimental animal studies and clinical trials suggests that endothelial progenitor cell (EPC) transplantation can repair “broken” heart by involving direct angiogenesis and secreting protective paracrine factors, which has a bright prospect for clinical application. However, transplantation of autologous EPC has numerous limitations, including the limited supply of expanded EPC, the impaired function and activity of the transplanted cells, and so on. Therefore, it is desirable to develop novel proangiogenic strategies that improve the efficacy of EPC transplantation.

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Small Trial Paves Way for Larger Study of Fat-Derived Stem Cells for Heart Failure

MedicalResearch.com Interview with:

Timothy D. Henry, MD, MSCAI Director, Division of Cardiology Cedars-Sinai Heart Institute

Dr. Timothy Henry

Timothy D. Henry, MD, MSCAI
Director, Division of Cardiology
Cedars-Sinai Heart Institute 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Henry: Heart failure it the #1 cause of morbidity, mortality and cost in the United States today.  Patients with Class 3 heart failure, despite optimal medical therapy and device therapy have limited options beyond heart transplantation and left ventricular cyst device.

Transplantation and LVAD are expensive and are challenged by both availability and complications.  Therefore, treatment for patients with ongoing symptoms despite medical therapy is an admiral goal.  Stem cell therapy appears to be an attractive choice for these patients, in particular patients with ischemic cardiomyopathy.

The ATHENA trial was designed to treat patients with ischemic cardiomyopathy and ongoing ischemia with autologous adipose-derived regenerative cells.  Patients would undergo liposuction with onsite processing of their stem cells in 1 ½ – 2 hours, followed by intramyocardial injection of adipose-derived regenerative cells (ADCRs) vs. placebo.

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Scientists Rejuvenate Old Stem Cells With Common Vitamin

MedicalResearch.com Interview with:

Keir Menzies PhD Assistant Professor  University of Ottawa Brain and Mind Research Institute University of Ottawa

Dr. Keir Menzies

Keir Menzies PhD
Assistant Professor
University of Ottawa Brain and Mind Research Institute
University of Ottawa 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Menzies: Currently there is significant amount of research identifying the power of stem cells to regenerate damaged or aging tissue. Our research discovered that reduced stem cell health was linked to unusually low levels of a small molecule called NAD, one of the most important cellular molecules to maintain the performance of mitochondria, the engine of the cell. Then by boosting NAD levels, using a special form of vitamin B3 called nicotinamide riboside, stem cells could be rejuvenated during aging by improving mitochondrial function.  We then go on to show that by improving stem cell function we could prolong the lifespan of mice, even when the treatment began at a relatively old age.

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Scientists Generate Functional Skin From Stem Cells

MedicalResearch.com Interview with:
Takashi Tsuji, PhD
Team Leader of  Laboratory for Organ Regeneration
RIKEN Center fo
r Developmental Biology
Chuo-ku, Kobe, Hyogo Japan

MedicalResearch.com: What was the impetus for this research? What made you think about creating a skin model?

Answer. Previously, we successfully demonstrated the functional organ regeneration including tooth (PNAS 2009), hair follicles (Nature Communications 2012), salivary gland (Nature Communications 2013a) and lachrymal gland (Nature Communications 2013b). We focused onto a complex organogenesis through the epithelial and mesenchymal cell interaction. In the current study as a continuous work, we would like to regenerate organ system by using multipotent stem cells such as ES and iPS cells. In this study, we first demonstrated the generation of a functional bioengineered 3D integumentary organ system from murine iPS cells.

MedicalResearch.com: Can you describe what you created in layperson terms? How big is it, what does it look like and what is it capable of doing?

Answer. We succeeded to demonstrate the proof-of-concept to generate 3D integumentary organ system, complete skin, which has skin appendages such as hair follicle and sebaceous gland, by mimicking the organogenesis during embryogenesis. In this work, we performed in murine system, so, the transplantable skin size is small as 1 mm2 /1 site. We think that further studies for humanization and the development of in vitro culture system would lead to realize of clinical applications for severe burned patients and severe hair loss. Furthermore, this method will contribute to understand the onset of dermoid tumor, which has ectodermal organs such as tooth and hair follicle, in human.

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Stem Cells Vary Widely Depending on Location and Donor Age

MedicalResearch.com Interview with:

Dr. Andrew Jaffe PhD Investigator, Lieber Institute for Brain Development Assistant Professor Wendy Klag Center for Autism and Developmental Disabilities Johns Hopkins Bloomberg School of Public Health

Dr. Andrew Jaffe

Dr. Andrew Jaffe PhD
Investigator, Lieber Institute for Brain Development
Assistant Professor
Wendy Klag Center for Autism and Developmental Disabilities
Johns Hopkins Bloomberg School of Public Health

Medical Research: What is the background for this study? What are the main findings?

Dr. Jaffe: Significant investments are being made worldwide in precision medicine, with much of the investment concentrated in the curation of stem cell lines for the generation of new tissues and organs. The most popular cell types for generating patient-specific stem cells are skin-derived and therefore receive potentially the highest amount of environmental exposure.

In our study, we were interested in characterizing the genomic variability in fibroblast cells from two locations in the body across the lifespan. The two locations were the scalp, which is exposed to the environment, and the dura mater, which is the membrane under the skull and is largely protected from environmental insult. While the fibroblast cells from these two locations look indistinguishable under a microscope, we found widespread epigenetic and expression differences between the cells related to where they came from in the body and also related, to a lesser extent, to the age of the donor.

As the field of personalized medicine continues to grow, this evidence necessitates further exploration into the epigenetic patterns in stem cells used for new tissue and organ generation. Additional research is required to determine which cells to cultivate and when, as researchers question how much epigenetic memory is actually erased when creating stem cell models.

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New Teeth: Why Can’t We Be More Like Sharks?

MedicalResearch.com Interview with:

Shark Teeth: lower jaw with 4 tooth rows and 4 tooth series labeled. "Series 1" contains the functional teeth at the front of the jaw. Wikipedia Image

Shark Teeth: lower jaw with 4 tooth rows and 4 tooth series labeled. “Series 1” contains the functional teeth at the front of the jaw. Wikipedia Image

Gareth J. Fraser, Ph.D
Lecturer in Zoology
Department of Animal and Plant Sciences
Alfred Denny Building
University of Sheffield
Western Bank Sheffield UK

MedicalResearch: What is the background for this study? What are the main findings?

 

 

Dr. Fraser: Our study shows how sharks develop their formidable, continuously regenerative conveyor belt-like dentition. We show how sharks make and regenerate their teeth utilising a core set of highly conserved genes shared among all vertebrates, including humans. This network of genes has been making teeth in vertebrates for over 400 million years. This report suggests that all teeth are made with this same group of genes. Sharks have an incredible ability to rapidly regenerate their dentition throughout life, and these genes are essential for this process of regeneration.

If we compare this process to mammals where the regenerative system is greatly reduced with only two sets of teeth, then we can begin to understand why humans have lost the ability to regenerate their dentition more than once. The beauty of studying natural systems like the shark dentition is that we can learn the basic science behind how teeth are naturally regenerated. This is important to human dental health as we can use these natural systems of tooth regeneration to learn about the essential cells and genes that regulate the process of natural tooth regeneration.

In the future, this research could facilitate the development of new dental therapies helping humans to regrow natural teeth when required.

Citation:

Liam J. Rasch, Kyle J. Martin, Rory L. Cooper, Brian D. Metscher, Charlie J. Underwood, Gareth J. Fraser. An ancient dental gene set governs development and continuous regeneration of teeth in sharks.
Developmental Biology, 2016; DOI:10.1016/j.ydbio.2016.01.038

Dr. Gareth Fraser (2016). New Teeth: Why Can’t We Be More Like Sharks? 

Radiation Converts Some Resistant Head and Neck Cancer Cells Into Aggressive Stem Cells

MedicalResearch.com Interview with:

Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714

Dr. Erina Vlashi

Erina Vlashi, PhD
Assistant Professor
Department of Radiation Oncology
David Geffen School of Medicine at UCLA
Los Angeles, CA 90095-1714

Medical Research: What is the background for this study? What are the main findings?

Dr. Vlashi: It has been known for quite some time that head and neck squamous cell carcinomas (HNSCC) that test positive for human papilloma virus (HPV) respond to radiation therapy more favorably than HPV-negative HNSCCs. Our team reviewed a cohort of 162 patients with a head and neck squamous carcinoma diagnosis over a two-year period, and confirmed that the outcomes were correlated with the patient’s HPV status. The work that followed was prompted by a discovery we had made earlier in breast cancer suggesting that breast cancer cells that manage to survive radiation therapy have the capacity to convert into more de-differentiated, therapy-resistant cells with characteristics of cancer stem cells, and that the degree of this conversion depended on the type of breast cancer: the more aggressive types of breast cancer being more prone to the therapy-induced phenotype conversion. So, we hypothesized that this therapy-induced conversion phenomenon may especially be at play in  head and neck squamous cell carcinomas given the clinical observation that HPV-positive HNSCCs respond to radiation therapy much more favorably than HPV-negative HNSCCs, despite optimum treatment modalities. And indeed, that is what we found: tumor cells derived from a panel of  head and neck squamous cell carcinomas cell lines that do not respond well to radiation therapy have an enhanced ability to convert the cells that survive radiation into more aggressive cells, cancer stem-like cells that will resist the next round of radiation therapy.  Continue reading

Stem Cell Derived Growth Factors May Slow Progression of ALS

Prof. Dimitrios Karussis M.D., Ph.D. Professor of Neurology Head, Multiple Sclerosis Center Hadassah BrainLabs

Prof. Dimitrios Karussis

MedicalResearch.com Interview with:
ProfDimitrios Karussis M.D., Ph.D.
Professor of Neurology
Head, Multiple Sclerosis Center
Hadassah BrainLabs

Medical Research: What is the background for this study? What are the main findings?

Prof. Karussis: BrainStorm Cell Therapeutics is developing innovative, autologous stem cell therapies for highly debilitating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD).  Our technology, NurOwn™ is a first-of-its-kind approach that induces autologous bone marrow-derived Mesenchymal Stem Cells (MSCs) to secrete Neurotrophic Growth Factors (NTFs).  These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases.

Data from the clinical trials described in the recent issue of the Journal of American Medicine – Neurology (JAMA Neurology), suggest that NurOwn can help patients with ALS.  The two trials featured in the article, a phase 1/2 and a phase 2a, studied the transplantation NurOwn cells in ALS patients.  These trials confirmed the excellent safety profile of NurOwn and suggest a clinically meaningful effect. The investigators used two well established clinical endpoints that measure disease activity in ALS, the Revised ALS Functional Rating Scale and Forced Vital Capacity, and were able demonstrate a slowing of disease activity in the period following treatment.

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Cancer Stem Cells May Facilitate Recurrent and Metastatic Breast Cancer

Jenny C. Chang, M.D. Director, Houston Methodist Cancer Center Professor of Medicine, Weill Cornell Medical College Full Member, Houston Methodist Research Institute Houston, Texas

Dr. Jenny C. Chang

MedicalResearch.com Interview with:
Jenny C. Chang, M.D.
Director, Houston Methodist Cancer Center
Professor of Medicine, Weill Cornell Medical College
Full Member, Houston Methodist Research Institute
Houston, Texas 

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Chang: The current treatment of triple negative breast cancer, which accounts for about 15% of all cases of breast cancer, is still based on surgery, radiotherapy, and classic chemotherapy because, unlike other types of breast cancer, it is not amenable to hormonal or targeted therapy. However, research findings suggest that cancer stem cells, which represent about 2% of all neoplastic cells, may play a role in disease relapses and the formation of distant metastases. As these cells may represent a therapeutic target, the aim of this study is to modify the micro-environment in which they reproduce by acting directly on the chemokines involved in inflammation because there is evidence indicating a possible mechanism of action of reparixin, a molecule developed by Dompé, an Italian biopharmaceutical company, in the targeted treatment of these cancers.

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Scientists Grow Liver Cells In Lab, Paving Way For Artificial Liver

Prof. Yaakov Nahmias Director of the Alexander Grass Center for Bioengineering Hebrew University of Jerusalem

Dr. Nahmias

MedicalResearch.com Interview with:
Prof. Yaakov Nahmias PhD
Director of the Alexander Grass Center for Bioengineering
Hebrew University of Jerusalem

Medical Research: What is the background for this study?

Prof. Nahmias: The liver has a limitless capacity of the human liver to regenerate from even a massive loss of mass.

However, the intrinsic capacity of liver cells to proliferate is lost when cells are removed from the body.

Medical Research: What are the main findings?

Prof. Nahmias: We found that a weak expression of Human Papilloma Virus (HPV) proteins released hepatocytes from cell-cycle arrest and permitted the cells to multiply in response to Oncostatin M (OSM) an immune cytokine recently found to be involved in liver regeneration.

While previous efforts caused hepatocytes to multiply without control, converting hepatocytes  into tumor cells with little metabolic ability, we selected colonies that only multiply in response to OSM.

Activation with OSM triggered cell growth with a doubling time of 40 hours. Removal of OSM caused  growth to stop, allowing the cells to regain a high level of metabolic activity within 4 days.

We produced hepatocytes from ethnically diverse individuals. Importantly, the growing hepatocytes  showed a similar toxicology response to normal human hepatocytes across 23 different drugs.

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Improved Stem Cell Model Can Test Drugs For Kidney Toxicity

Daniele Zink PhD Institute of Bioengineering and Nanotechnology Singapore

Dr. Zink

MedicalResearch.com Interview with:
Daniele Zink PhD
Institute of Bioengineering and Nanotechnology
Singapore 

Medical Research: What is the background for this study?

Dr. Zink: The kidney is one of the main target organs for toxic effects of drugs, environmental toxicants and other compounds. Renal proximal tubular cells (PTCs) are frequently affected due to their roles in compound transport and metabolism. Validated and accepted assays for the prediction of PTC toxicity in humans currently do not exist. Recently, we have developed the first and only pre-validated assays for the accurate prediction of PTC toxicity in humans 12. This previous work was performed with human primary renal proximal tubular cells (HPTCs) or embryonic stem cell-derived HPTC-like cells. HPTCs are associated with a variety of issues that apply to all kinds of primary cells, such as cell sourcing problems, inter-donor variability and limited proliferative capacity. Embryonic stem cell-derived cells are associated with ethical and legal issues. These are the main reasons why induced pluripotent stem cell (iPSC)-derived cells are currently a favored cell source for in vitro toxicology and other applications.

The problem was that stem cell-based approaches were not well-established with respect to the kidney. Recently, the group of IBN Executive Director Prof. Jackie Y. Ying developed the first protocol for differentiating embryonic stem cells into HPTC-like cells, and my group has contributed to characterizing these cells and publishing the results 3.  In the work published in Scientific Reports ,4we have applied a modified version of this protocol to iPSCs. In this way, we have established the simplest and fastest protocol ever for differentiating iPSCs into HPTC-like cells. The cells can be used for downstream applications after just 8 days of differentiation. These cells can also be applied directly without further purification due to their high purity of > 90%.

By using these cells, we have developed the first and only iPSC-based model for the prediction of PTC toxicity in humans. This was achieved by combining our iPSC-based differentiation protocol with our previously developed assay based on interleukin (IL)6/IL8 induction 12 and machine learning methods 5. Machine learning methods were used for data analysis and for determining the predictive performance of the assay. The test accuracy of the predictive iPSC-based model is 87%, and the assay is suitable for correctly identifying injury mechanisms and compound-induced cellular pathways.

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Gene-edited Kidney Organoids Re-Create Human Disease

Benjamin Freedman, Ph.D. Assistant Professor | University of Washington Department of Medicine | Division of Nephrology Member, Kidney Research Institute Member, Institute for Stem Cell and Regenerative Medicine Seattle WA 98109

Dr. Benjamin Freedman

MedicalResearch.com Interview with:
Benjamin Freedman, Ph.D.

Assistant Professor | University of Washington
Department of Medicine | Division of Nephrology
Member, Kidney Research Institute
Member, Institute for Stem Cell and Regenerative Medicine
Seattle WA 98109 

Medical Research: What is the background for this study? What are the main findings?

Dr. Freedman: We are born with a limited number of kidney tubular subunits called nephrons. There are many different types of kidney disease that affect different parts of the nephron. The common denominator between all of these diseases is the irreversible loss of nephrons, which causes chronic kidney disease in 730 million patients worldwide, and end stage renal disease in 2.5 million. Few treatments have been discovered that specifically treat kidney disease, and the therapeutic gold standards, dialysis and transplant, are of limited availability and efficacy.

Pluripotent stem cells are a renewable source of patient-specific human tissues for regeneration and disease analysis. In our study, we investigated the potential of pluripotent cells to re-create functional kidney tissue and disease in the lab. Pluripotent cells treated with a simple chemical cocktail matured into mini-kidney ‘organoids’ that closely resembled nephrons. Using an advanced gene editing technique called CRISPR, we created stem cells with genetic mutations linked to two common kidney diseases, polycystic kidney disease (PKD) and glomerulonephritis. Mini-kidneys derived from these genetically engineered cells showed specific ‘symptoms’ of these two different diseases in the petri dish.

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Attacking Pancreatic Cancer Stem Cells May Lead To Better Treatment

Patricia Sancho, PhD, Lecturer Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London EC1M 6BQMedicalResearch.com Interview with:
Patricia Sancho, PhD, Lecturer

Barts Cancer Institute – a Cancer Research UK Centre of Excellence
Queen Mary University of London
Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London

Medical Research: What is the background for this study? What are the main findings?

Dr. Sancho: Cancer cells commonly rely on glycolysis, the type of metabolism that does not use oxygen to generate their energy however, we have now found that not all cancer cells are alike when it comes to metabolism. Pancreatic Cancer Stem cells (PancCSCs) can make use of a more efficient form of metabolism, called oxidative phosphorylation or OXPHOS, which does use oxygen. OXPHOS uses a part of the cell called mitochondria and it is this which can be targeted with anti-diabetic drug, metformin. Some PancSCs are however able to escape this treatment by being much more flexible in their metabolism, leading to a recurrence of the cancer, but we also found a way to prevent such resistance and force all Pancreatic Cancer Stem cells to keep using OXPHOS.

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Patient-Derived Stem Cells May Be Able To Reverse Hemophilia A

Dong-Wook Kim Center for Genome Engineering, Institute for Basic Science Yonsei University College of Medicine Seoul, KoreaMedicalResearch.com Interview with:
Dong-Wook Kim
Center for Genome Engineering, Institute for Basic Science
Yonsei University College of Medicine
Seoul, Korea

Medical Research: What is the background for this study?

Response: Hemophilia A is an X-linked genetic disorder caused by mutations in the F8 gene, which encodes the blood coagulation factor VIII. Almost half of all severe hemophilia A cases result from two gross (140-kbp or 600-kbp) chromosomal inversions. We derived induced pluripotent stem cells (iPSCs) from patients with these inversion genotypes and used CRISPR-Cas9 nucleases to revert these chromosomal segments back to the WT situation.

Medical Research: What are the main findings?

Response: We isolated inversion-corrected iPSCs with frequencies of up to 6.7% without detectable off-target mutations based on whole-genome sequencing or targeted deep sequencing. Endothelial cells differentiated from corrected iPSCs expressed the F8 gene and functionally rescued factor VIII deficiency in an otherwise lethal mouse model of hemophilia.

Medical Research: What should clinicians and patients take away from your report?

Response: Our results provide a proof of principle for functional correction of large chromosomal inversions in Hemophilia patient-derived induced pluripotent stem cells and suggest potential therapeutic applications in the future.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: We need to prove the safety of patient-derived iPSCs before we move towards clinics.

The safety of iPSCs means to prevent teratoma formation when we do clinical trials.

For that purpose, we need to develop good differentiation protocols into EC cells and to purify the cells as well. In addition, we need much more animal study.

Citation:

Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9

Chul-Yong Park Duk Hyoung Kim Jeong Sang Son Jin Jea Sung Jaehun Lee Sangsu Bae Jong-Hoon Kim Dong-Wook Kim Jin-Soo Kim

Cell Stem Cell Available online 23 July 2015

doi:10.1016/j.stem.2015.07.001

Dong-Wook Kim (2015). Patient-Derived Stem Cells May Be Able To Reverse Hemophilia

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Random Stem Cell Divisions May Play Role in Persistent HPV Infections

Marc Ryser PhD Visiting Assistant Professor Department of Mathematics Duke University Durham, North CarolinaMedicalResearch.com Interview with:
Marc Ryser PhD
Visiting Assistant Professor Department of Mathematics
Duke University Durham, North Carolina

Medical Research: What is the background for this study

Dr. Ryser: Infection with the human papillomavirus (HPV) is responsible for approximately 5% of all cancers worldwide. In addition to cervical cancers, HPV is associated with various other female and male cancers, including cancers of the anus and oropharynx. Despite expansive screening and vaccination programs, HPV-related cancers remain a serious public health concern in the US and abroad. To further improve public health interventions against HPV, a thorough understanding of the underlying biology is critical.

The lifetime risk of getting infected with HPV is as high as 80%, yet most individuals remain asymptomatic and clear the virus after 1-2 years.  However, if an infection with a high-risk type of HPV persists, the virus can interfere with the replication mechanism of the host cells, and initiate tumor growth. Even though our understanding is incomplete to date, clearance of HPV infections is primarily attributed to an effective immune response.

Interestingly, recent studies about the stem cell dynamics in epithelial tissues – the types of tissues that are affected by HPV –  have shown that the fate of these stem cells is random: most of the time, a stem cell divides into a new stem cell and a differentiating daughter cell; however, every now and then, a stem cell divides either into two stem cells, or into two differentiating daughter cells. These dynamics have not been acknowledged by the HPV community, and our goal was to develop mathematical models to examine whether the random division patterns of stem cells could play a role in the clearance of HPV infections.
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Research Suggests Neural Stem Cells Have Brief LIves

MedicalResearch.com Interview with Filippo Calzolari PhD Institute of Stem Cell Research, ISF-N Helmholtz Zentrum München Neuherberg GermanyMedicalResearch.com Interview with Filippo Calzolari PhD
Institute of Stem Cell Research, ISF-N
Helmholtz Zentrum München
Neuherberg Germany

 

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Calzolari: Despite their amazing complexity, life-long production of new neurons occurs in only a few well-circumscribed areas in adult mammalian brains, thanks to the activity of adult Neural Stem Cells (NSCs). How  Neural Stem Cells in these regions maintain neuronal production throughout life is however poorly understood, due in part to the difficulty of assessing the behavior of single stem cells, in vivo.

Our work now partially fills this gap, by providing a description of how single  Neural Stem Cells of the mouse subependymal zone (SEZ) generate new neurons destined to the olfactory bulb (OB).

In the SEZ, only a small proportion of  Neural Stem Cells are active at any given time, and single stem cells sustain neurogenesis in a rather “bursty” manner, often generating more than a hundred immature neurons within a few weeks.  Given such dynamism, it came as a surprise to note that most NSCs became exhausted after a few weeks of starting their activity, thus failing to show a crucial hallmark of “stemness”, i.e. the ability to extensively self-renew. Interestingly, each  Neural Stem Cell mostly produced only one of the various subtypes of neurons that make up the adult-generated olfactory bulb neuronal population. These new data thus indicate that both long-term adult neuron generation and the production of a diverse set of neurons are the cumulative result of a population of individually short-lived and subtype-restricted “stem cells”.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Calzolari: Ours is a rather basic description of a biological process, and it is therefore “risky” to come up with catchy messages for clinicians and patients alike. However, a notion that should stick is that aging may be associated with the progressive loss, rather than drift to quiescence, of neural stem cells. Therefore, trying to preserve stem cell numbers over time may be a useful preventive strategy, should any late regenerative response need to be elicited. It´s clear however that a lot needs to be figured out in order to safely attempt such a strategy.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Calzolari: A crucial step will be to figure out the molecular basis for the rather brief nature of neural stem cells activity. Can neuron production from a single NSC be prolonged safely?

Maybe even more crucial, it will be to find out how much our observations apply to humans. Are our Neural Stem Cells as short-lived as mouse ones?

Citation:

Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone
Filippo Calzolari, Julia Michel,Emily Violette Baumgart, Fabian Theis, Magdalena Götz

& Jovica Ninkovic Nature Neuroscience (2015)

doi:10.1038/nn.3963

 

MedicalResearch.com Interview with Filippo Calzolari PhD (2015). Research Suggests Neural Stem Cells Have Brief LIves 

Scientists Complete First Steps Toward Making Sperm and Eggs From Skin Stem Cells

Jacob (Yaqub) Hanna  M.D. Ph.D. Kimmel Investigator | NYSCF Robertson Investigator The Department of Molecular Genetics Weizmann Institute of Science, IsraelMedicalResearch.com Interview with:
Jacob (Yaqub) Hanna  M.D. Ph.D.
Kimmel Investigator | NYSCF Robertson Investigator
The Department of Molecular Genetics
Weizmann Institute of Science, Israel

MedicalResearch: Could this be helpful for any individual with infertility problems? 

Dr Hanna: Our research is focused on taking skin cell samples and converting them into embryonic-like stem cells (iPS cells) via direct reprogramming and without using embryo derived stem cell lines. Then we are focusing in differentiating these male or female iPS lines into sperm cells or oocytes, respectively. We have succeeded in the first and most important step of the process, where we succeed in reaching the progenitor cell state for sperm and egg (we have not achieved mature sperm and eggs ….Very important to emphasize!). So we are now focusing on completing the second half of this process. Once that is achieved this may become useful for any individual with fertility problems.

MedicalResearch: Could this be a viable option ALSO for same-sex couples?  What are the prospects for letting gay or lesbian couples produce progenitor cell state cells from their skin cells? For example, is it conceivable that the “second half” of the protocol could some day also be done in vitro (making fully mature sperm and eggs), so that men could produce egg cells and women sperm cells?
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Lab Turns Stem Cells Into Hair Bulbs That Grow Hair

Alexey Terskikh, Ph.D. Associate Professor Department of Developmental and Stem Cell Biology Sanford-Burnham Medical Research Institute La Jolla, CAMedicalResearch.com Interview with:
Alexey Terskikh, Ph.D. Associate Professor
Department of Developmental and Stem Cell Biology
Sanford-Burnham Medical Research Institute
La Jolla, CA

Medical Research: What is the background for this study? What are the main findings?

Dr. Terskikh: Hair loss is a wide spread human condition with an unmet need for hair replacement. In the United States alone, over 40 million men and 21 million women are affected by hair loss. I have been interested in the differentiation of human pluripotent stem cells into various cell including neural crest cells. In-vivo neural crest cells give rise to a multitude of cell types, including dermal papilla cells, which populate the bulb of hair follicles and regulate hair growth. We have established new method to differentiate human pluripotent stem cells into dermal papilla-like (DP-like) cells, with a goal of inducing hair growth. To find out whether DP-like cells induce hair growth we transplanted these cells under the skin of mice (which have a small amounts of white hair) along with the skin cells from dark-haired mice. We observed the growth of new black hairs suggesting the induction of hair growth by transplanted human DP-like cells.

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Stem Cells Can Be Grown From Blood Of Deceased Patients

Dr. Dhruv Sareen, PhD Director, iPSC Core Facility Regenerative Medicine Institute Research Scientist, Neurobiology Research Cedars-Sinai, Los Angeles CAMedicalResearch.com Interview with:
Dr. Dhruv Sareen, PhD
Director, iPSC Core Facility
Regenerative Medicine Institute
Research Scientist, Neurobiology Research
Cedars-Sinai, Los Angeles CA

Medical Research: What is the background for this study? What are the main findings?

Dr. Sareen: We have developed a novel method to re-create brain and intestinal stem cells from patients who died decades ago, using stored blood samples. Using the iPS cell technology at Cedars-Sinai this new method now allows us to apply to alive as well as deceased patient blood cells. Our study, published in the journal STEM CELLS Translational Medicine, highlights the power of this technology for many deceased patients that were diagnosed with debilitating diseases, such as inflammatory bowel disease (IBD) and motor neuron diseases (spinal muscular atrophy and ALS). Patients had their blood samples stored away at Cedars-Sinai when they were alive decades ago. At that time all researchers could have done was collect and bank their blood cell lines for research purposes. The iPS cell technology wasn’t even on scientists radar then. With novel developments in my lab we have figured out how to reliably create new stem cell lines from patient blood samples stored away in large cell banks. We have also shown that these recreated stem cells can efficiently make neurons specific to the spine (motor) and cells of the gut. Since it is very difficult to get unlimited access to research affected cells and tissues from the patients, our discoveries now allow us such important capabilities. Thus, now we are not limited to animal models of disease, but can use these patient-specific stem cells to better pinpoint potential causes of these devastating illnesses.

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Mesenchymal Stem Cells Did Not Prevent Kidney Injury After Heart Surgery

Madhav Swaminathan, MBBS, MD, FASE, FAHA Associate Professor with Tenure Clinical Director, Division of Cardiothoracic Anesthesiology & Critical Care Medicine Department of Anesthesiology Duke University Health System Durham, NC 27710MedicalResearch.com Interview with:
Madhav Swaminathan, MBBS, MD, FASE, FAHA
Associate Professor with Tenure
Clinical Director, Division of Cardiothoracic Anesthesiology & Critical Care Medicine Department of Anesthesiology
Duke University Health System Durham, NC 27710

Medical Research: What is the background for this study? What are the main findings?

Dr. Swaminathan: The background is the need for salvage therapies for acute kidney injury (AKI,) which is a common complication in hospitalized patients. It is particularly a problem in the postoperative period after cardiac surgery. Preventive strategies have not worked well for decades. Hence the focus on strategies that target kidney recovery. Mesenchymal stem cells have been shown to be useful in enhancing kidney recovery in pre-clinical trials. We therefore hypothesized that administration of human Mesenchymal stem cells (AC607, Allocure Inc, Burlington, MA) to patients with established post-cardiac surgery AKI would result in a shorter time to kidney recovery. We conducted a phase 2, double blinded, placebo controlled, randomized clinical trial to test our hypothesis. Unfortunately we could not confirm the hypothesis and there were no significant differences in time to kidney recovery among patients that received AC607 versus placebo in 156 randomized cardiac surgery subjects.

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Skin Cells Converted Into Neurons That Affect Huntington’s Disease

MedicalResearch.com Interview with:
Matheus Victorm PhD candidate
Dr. Andrew Yoo’s Lab
Graduate Program in Neuroscience
Washington University School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Answer: We have described a way to convert human skin cells directly into a specific type of brain cell called medium spiny neurons that is affected by Huntington’s disease, an ultimately fatal neurodegenerative disorder. Unlike other techniques that turn one cell type into another, this new process does not pass through a stem cell phase. Furthermore, we demonstrated that these converted cells survived at least six months after injection into the brains of mice and behaved similarly to native cells in the brain. Not only did these transplanted cells survive in the mouse brain, they showed functional properties similar to those of native cells. These cells are known to extend projections into certain brain regions and we found the human transplanted cells also connected to these distant targets in the mouse brain.

Medical Research: What should clinicians and patients take away from your report? What recommendations do you have for future research as a result of this study?

Answer:  The generation of a highly enriched population of medium spiny neurons allows the possibility of dissecting the pathogenesis of Huntington’s disease in a dish. This will enable researchers to investigate potential new drugs or small molecules that could be used to treat patients suffering from this disorder.To study the cellular properties associated with the disease, we are now taking skin cells from patients with Huntington’s disease and reprogramming them into medium spiny neurons using the approach described in the new paper. We also plan to inject healthy  reprogrammed human cells into mice with a model of Huntington’s disease to see if this has any effect on the symptoms.

Citation:

Generation of Human Striatal Neurons by MicroRNA-Dependent Direct Conversion of Fibroblasts

Matheus B. Victor,Michelle Richner, Tracey O. Hermanstyne, Joseph L. Ransdell, Courtney Sobieski, Pan-Yue Deng, Vitaly A. Klyachko, Jeanne M. Nerbonne, Andrew S. Yoo

Neuron DOI: http://dx.doi.org/10.1016/j.neuron.2014.10.016

 

 

Study Examines Risk of Alopecia Areata and Vitiligo in Stem Cell Recipients

MedicalResearch.com Interview with:
Rena Zuo, BA
MD Candidate at Duke University School of Medicine and

Edward W. Cowen, MD, MHSc
Senior Clinician
Head, Dermatology Consultation Service
Dermatology Branch
Center for Cancer Research National Cancer Institute
National Institutes of Health

MedicalResearch: What are the main findings of the study?


Answer: Chronic graft-vs-host disease (cGVHD) is a debilitating multisystem disease that occurs in patients receiving allogeneic hematopoietic stem cell transplantations as treatment for hematologic disorders. Although the diverse clinical presentations of cGVHD frequently mimic other autoimmune diseases such as Sjögren syndrome and systemic sclerosis, and low-titer antibodies are commonly found in patients with cGVHD, the exact pathogenesis and role of autoimmunity in cGVHD are incompletely understood.

Our study is the first to characterize and identify risk factors associated with the development of two uncommon autoimmune phenomena, specifically alopecia areata and vitiligo, in the setting of cGVHD. Laboratory markers, including 11 antibodies, transplant-related factors, and other cGVHD systemic manifestations were analyzed.

Several particularly interesting results were found:

  1. Among 282 patients with cGVHD, 15 demonstrated vitiligo (14 of 282; 4.9%) and/or alopecia areata (2 of 282; 0.7%).
  2. Female donor and female donor to male recipient sex mismatch, in particular, are significantly associated with the development of vitiligo and/or alopecia areata.
  3. Positive anti-cardiolipin (ACA) IgG was also significantly associated with development of vitiligo and/or alopecia areata.

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Coronary Arteries Supply Stem Cells To Generate New Heart Muscle

Antonis Hatzopoulos, PhD, FAHA Associate Professor of Medicine- Division of Cardiovascular Medicine  Associate Professor of Cell & Developmental Biology Vanderbilt Center for Stem Cell Biology Vanderbilt University  Nashville, TN 37232-6300MedicalResearch.com Interview with:
Antonis Hatzopoulos, PhD, FAHA
Associate Professor of Medicine- Division of Cardiovascular Medicine
Associate Professor of Cell & Developmental Biology
Vanderbilt Center for Stem Cell Biology
Vanderbilt University
Nashville, TN 37232-6300
Medical Research: What are the main findings of the study?

Dr. Hatzopoulos: Using cell tracking in the normal adult mouse heart, we found that endothelial cells can function as cardiac stem cells to generate new heart muscle.  Our results show that besides heart muscle, endothelial cells produce quiescent and proliferating cardiac progenitor cells that reside in the media and adventitia layers of the coronary arteries, respectively.
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Stem Cells May Give Hope To Patients With Severe Stroke Disability

MedicalResearch.com Interview with:
Dr Soma Banerjee M.D.
Department of Stroke Medicine
Imperial College Healthcare National Health Services Trust
St. Mary’s Hospital Campus, Praed Street, London

Medical Research: What are the main findings of the study?

Dr. Banerjee: This stem cell trial is the first of its kind in humans to show that selected bone marrow stem cells (CD34+ cells) from the patients’ own bone marrow, can be administered to patients with severe strokes, within an early timescale after their stroke.

This pilot study of 5 patients showed that it was both safe and feasible to administer these cells to patients within a week of the event.

This was primarily a safety study, but clinical measures of recovery were also assessed, and these showed improvements in disability scores and scores of neurological impairment, in all 5 patients.
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Study Uses Dental Stem Cells To Promote Retinal Regeneration After Eye Injury

Ben Mead Molecular Neuroscience Group Neurotrauma and Neurodegeneration Section School of Clinical and Experimental Medicine University of Birmingham, BirminghamMedicalResearch.com Interview with:
Ben Mead
Molecular Neuroscience Group
Neurotrauma and Neurodegeneration Section
School of Clinical and Experimental Medicine
University of Birmingham, Birmingham

Medical Research: What are the main findings of the study?

Answer: Traumatic and neurodegenerative disease of the retina lead to an irreversible loss of retinal ganglion cells (RGC) which are the neuronal cells located in the inner retina that transmit visual signals to the brain. Thus RGC injury results in visual defects which can ultimately progress into permanent blindness. One promising therapeutic approach is the use of stem cells as a source of replacement for lost retinal cells. However a theory has emerged suggesting that stem cells can act through the secretion of signalling molecules (growth factors). One stem cell that has recently shown great promise for neuronal repair are dental pulp stem cells (DPSC), which are multipotent stem cells easily isolated from adult teeth, including third molars (Mead et al 2013, 2014).

In our research, we transplanted either dental pulp stem cells or the more widely studied bone marrow-derived mesenchymal stem cell (BMSC) into the vitreous chamber of the eye after optic nerve crush (Mead et al 2013). The main finding of this study was that DPSC, to a significantly greater degree than BMSC, promoted the survival of injured RGC and the regeneration of their axons. We also showed that the mechanism of action was not through differentiation and replacement of cells but was actually paracrine mediated, i.e. through DPSC-derived growth factors (Mead et al, 2013, 2014).
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