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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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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Phase 3 Trial of Iomab-B as an Induction and Conditioning Agent Prior to Bone Marrow or Stem Cell Transplant in Relapsed or Refractory AML

MedicalResearch.com Interview with:

Felix Garzon, MD, PhD Senior Vice President Head of Clinical Development Actinium Pharmaceuticals, Inc. New York, NY 10016

Felix Garzon

Felix Garzon, MD, PhD
Senior Vice President
Head of Clinical Development
Actinium Pharmaceuticals, Inc.
New York, NY 10016

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

Response: Iomab-B (“Iomab”) was developed at the Fred Hutchinson Cancer Research Center (“the Hutch”) in Seattle, Washington. The Hutch is a pioneer in the field of bone marrow transplantation (BMT) having 3 Nobel Prizes and doctors there performed some of the first transplants for leukemia patients. Iomab-B is intended to be an induction and conditioning agent prior to a BMT for patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are over the age of 55. BMT is the only potentially curative option for AML i.e. for this patient population that currently has a survival prognosis of 2-6 months which means that if Iomab-B is successful it would create a new market segment and offer patients a great clinical benefit and a hope for a cure. Actinium Pharmaceuticals licensed Iomab from the Hutch in 2012 and prior to us licensing Iomab, it had been studied in almost 300 patients in several phase 1 and phase 2 clinical trials in an array of blood cancers, both leukemias and lymphomas. Actinium is now the sponsor of a pivotal phase 3 trial for Iomab-B to study its use as an induction and conditioning agent prior to a bone marrow transplantation in patients with relapsed or refractory AML who are over the age of 55. This trial, which we have named the SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial, started at the end of June 2016 and we expect to enroll 150 patients by the end of 2017.

The primary endpoint of the SIERRA trial is durable complete remissions (dCR) of 6 months. The study arm will consist of Iomab-B administration followed by a  bone marrow transplantation, patients will be evaluated for dCR at 6 months after engraftment, which will be assessed at day 28 or day 56. The control arm of the study will be physician’s choice of chemotherapy and if the patient is able to achieve a complete remission (CR) they may receive a BMT or some other form of treatment with curative intent. The study is designed to evaluate if the study arm of Iomab-B and a BMT can double the dCR rate of the control arm, which is designed to replicate the current treatment regimen prior to a bone marrow transplantation .

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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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HIV Lymphoma Patients Now Candidates For Stem Cell Transplants

MedicalResearch.com Interview with:

Joseph Alvarnas, MD Associate clinical professor Department of hematology and Director of value-based analytics City of Hope National Medical Center Duarte, CA

Dr. Joseph Alvarnas

Joseph Alvarnas, MD
Associate clinical professor
Department of hematology and Director of value-based analytics
City of Hope National Medical Center
Duarte, CA

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

Dr. Alvarnas: Patients with HIV infection have a significantly increased risk of non-Hodgkin lymphoma and Hodgkin lymphoma. Prior to the availability of effective anti-retroviral therapy, HIV-infected patients with lymphoma had very poor treatment outcomes. Following the availability of effective anti-HIV therapy, patient outcomes for HIV-infected patients now parallel those of non-infected patients. Historically, however, HIV infection has been used as a criterion for not offering patients autologous blood stem cell transplantation outside of centers with unique expertise. The purpose of this trial was to evaluate outcomes, complication rates, and immunological reconstitution of HIV-infected patients following autologous blood stem cell transplantation.
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Multiple Myeloma: Thalidomide Derivative Lenalidomide Improved Survival After Chemo and Stem Cell Transplant

MedicalResearch.com Interview with:

Philip McCarthy, BA, MD Professor of Oncology Director, Blood and Marrow Transplant Program Roswell Park Cancer Institute Associate Professor of Medicine Jacobs School of Medicine and Biomedical Sciences State University of New York at Buffalo Buffalo, NY 14263

Dr. Philip McCarthy

Philip McCarthy, BA, MD
Professor of Oncology
Director, Blood and Marrow Transplant Program
Roswell Park Cancer Institute
Associate Professor of Medicine
Jacobs School of Medicine and Biomedical Sciences
State University of New York at Buffalo
Buffalo, NY 14263

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

Dr. McCarthy: There have been three Phase III studies that examined the role of maintenance lenalidomide after autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma patients. IFM 2005-02 (France), CALGB 100104 (Alliance, USA), GIMEMA-RVMM-PI-209 (Italy). All three studies had progression free survival (PFS) as their primary endpoint and all demonstrated a superior PFS when compared to placebo or no therapy after ASCT. However only the CALGB 100104 study demonstrated a statistically superior overall survival (OS). Thus, a meta-analysis was necessary to assess the effect of post-ASCT lenalidomide maintenance on overall survival. This study utilized a pooled analysis of updated primary-source patient data from all three studies after the primary efficacy analyses had been conducted. The meta-analysis demonstrated that there is a statistically superior OS (P value=0.001, HR=0.74 (0.62-0.89)), Median OS for no maintenance or placebo was 86 months and the median OS for lenalidomide had not been reached. The median OS for lenalidomide treatment arm was extrapolated to be 116 months based on median of the control arm and HR (median, 86 months; HR = 0.74). Thus, there is a 26% reduction in the risk of death which is an estimated 2.5 year increase in median OS. There is an increased incidence of second primary malignancies with lenalidomide maintenance when compared to placebo but this risk is less than the risk of dying when not receiving lenalidomide.

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French Grape Seed Extract May Help Eliminate Cancer Stem Cells

MedicalResearch.com Interview with:
Ajay Goel, Ph.D.
Professor, and Director of Center for Epigenetics and Cancer Preventio
Baylor Scott & White Research Institute
Baylor University Medical Center, Dallas, TX

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

Dr. Goel: One of the areas in which I am interested is examining the activity of natural compounds as it relates to cancer prevention, progression, and treatment. Polyphenols have known antioxidant and anti-cancer activity, but it is important that we better understand the mechanisms of action. I have found in my research on curcumin and boswellia that these plants contain compounds that work on an epigenetic level and can influence microRNA in ways that chemotherapeutic agents cannot. MicroRNA is important because it is like a master control panel that turns on and off a multitude of genetic “switches.” Influencing the activity of microRNA influences a wide array of genetic expression. If you tell the general of the army what to do, it has a much greater impact than directions given to a private, because the general influences so many more soldiers.

Because grape seed extract contains oligomeric proanthocyanidins (OPC) that are also quite active in influential cancer mitigating genetic pathways, I wanted to determine its effects more exactly. I chose specifically tannin-free, low molecular weight OPCs because there is some evidence that the larger sized OPCs are not absorbable.

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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 May Improve Blood Flow In Patients With Erectile Dysfunction

MedicalResearch.com Interview with:

Dr. Michael Zahalsky MD Medical Director of Urological Oncology North Broward Medical Center, Florida

Dr. Michael Zahalsky

Dr. Michael Zahalsky MD
Medical Director of Urological Oncology
North Broward Medical Center, Florida

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

Dr. Zahalsky: Erectile dysfunction or the inability to maintain an erection satisfactory for sexual intercourse is a disease that affects hundreds of millions of men worldwide. Currently, the most utilized methods to help treat these men include oral medications, injectable medications and penile prostheses.

We sought out new alternatives to treat and potentially even cure erectile dysfunction by using stem cells and biologic-based therapies – treatments that are now being used in various fields of medicine from orthopedics to plastic surgery. We decided to see how their effect will influence Erectile Dysfunction by evaluating blood flow to the penis. In the past we studied Peyronie’s Disease using a similar treatment modality and showed that with a single injection blood flow improved, plaque size decreased, and penile curvature lessened.  There have been many animal studies, as well, showing the benefit of biologic-based therapies in the treatment of Erectile Dysfunction and Peyronie’s Disease.

We chose to use placental matrix derived mesenchymal stem cells in this study on Erectile Dysfunction. We had a small sample of 8 patients who underwent treatment. We had statistically significant increase in blood flow into the penis.  This was demonstrated by an increase in peak systolic velocity using color doppler on ultrasound.

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Using Small Carriers Increases Number of Cardiac Stem Cells Remaining in Heart

MedicalResearch.com Interview with:

Joost P.G. Sluijter, PhD, FESC Assistant Professor Department of Cardiology Experimental Cardiology Laboratory UMC Utrecht

Dr. Joost Sluijter

Joost P.G. Sluijter, PhD, FESC
Associate Professor
Department of Cardiology
Experimental Cardiology Laboratory
UMC Utrecht

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

Dr. Sluijter: Cell transplantation therapy for ischemic heart disease has entered the arena of clinical trials more than a decade ago. Multiple cell types have been used since these first endeavors, and there is accumulating evidence that different cell types positively influence the damaged heart through paracrine and/or regenerative mechanisms. One of the most promising cell types to be used are the cardiac-located stem cells. Cardiac stem cells (CSCs) have been found to reside in the adult heart and can differentiate towards all cell types that are needed in the normal functional heart. These cells have shown great potential as a regenerative therapeutic upon myocardial infarction (MI) in animal models and are currently being tested in some clinical studies. However, although promising, no systematic overview and subsequent meta-analysis of preclinical data exists to date for this cell type and if they are consistently effective. Our systematic approach, yielded 80 studies and included over 1900 animals, confirms the consistent effect of CSCs and provides us with a first comprehensive overview of pre-clinical MI studies in an unbiased and systematic manner.  Nowadays we are aware of a failure in therapeutic effect size for the translation axis, where we try to bridge fundamental findings from the lab to the bedside. This means that effects we observe in our initial studies on cardiac performance are slowly getting less successful when we are getting closer to a real clinical scenario.

Through our meta-analysis, we observed a consistent therapeutic effect of Cardiac stem cells therapy on cardiac function after MI, where 12% of functional improvements is observed in rodents, and only an 8% improvement was still present in large animal models. From previous observations, we know that this leaves a 3-4% of effect in a patient population. In addition to the difference in effect size between small and large animal models, also a difference in study quality and attrition bias was observed. Interestingly, although additional support to the idea that Cardiac stem cells are efficacious in preclinical studies were observed, we did not find any influence of immunosuppression, cell source, comorbidity of CSC donors, culture methods, or model of ischemia on the outcomes.

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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

Regrowing Axons Not Enough To Make Functional New Nerves

MedicalResearch.com Interview with:
Zhigang He, PhD, BM 
Professor of Neurology  and
Michela Fagiolini, PhD Assistant Professor of Neurology
F.M. Kirby Neurobiology Center, Department of Neurology
Children’s Hospital, Harvard Medical School
Boston, MA 02115, USA

Medical Research: What is the background for this study?

Drs. Fagiolini and He: Brain or spinal cord injury is still a major medical problem and there is no effective treatment of promoting functional recovery. A key issue is the nerve fibers, or axons, connecting different brain regions are damaged and cannot be repaired. For example, the axons in the optic nerve are the only channels transmitting visual signals from eye to brain. If damaged, our brain will not be able to receive visual signals and be blinded. Thus, a logical therapy should be to stimulate damaged axons to regrow to the targets and reconnect the eyes and brain. Studies in the past from us and others revealed several approaches of promoting the regrowth of injured axons, but it was unknown whether these regenerated axons could form functional connections and mediate functional recovery.

Medical Research: What are the main findings?

Drs. Fagiolini and He:  What we discovered in this study is that these regenerated axons could form functional connections, synapses, in the brain targets, but surprisingly fail to mediate behavioral visual function recovery. In mammals, many long projecting axons are insulated by lipid-enriched myelin sheets which could significantly speed up nerve conduction and facilitate the functional coordination of different brain regions during behavior. Interestingly, we found that different from intact optic nerves, these regenerated axons fail to be myelinated and thus possess poor conductance. When we treat these mice with compounds that can improve nerve conduction, we do observe partial yet significant functional recovery. Thus, there are at least two pieces of information from this study:

  • First, axon regrowth might not enough for functional recovery, nerve conduction could be another hurdle;
  • Second, the combination of these manipulations could serve a proof-of-principle example for achieving functional recovery.

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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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Stem Cell Therapy May Be Most Effective, and Most Toxic, Treatment For Crohn’s Disease

Dr. Chris J. Hawkey, DM, FRCP, FMedSci. University of Nottingham and Nottingham University Hospital England

Dr. Chris Hawkey

MedicalResearch.com Interview with:
Dr. Chris J. Hawkey, DM, FRCP, FMedSci.
University of Nottingham and Nottingham University Hospital
England

Medical Research: What is the background for this study?

 Dr. Hawkey: ASTIC (The Autologous Stem Cell Transplantation International Crohn’s Disease) systematically investigated the effect of immunoablation and autologous haemopoietic stem cell transplantation (HSCT) on objective signs of disease, symptoms and need for treatment and is the only controlled trial to have done so. The body’s immune system normally protects us from infections but in Crohn’s disease it turns on itself.  The treatment involves wiping out the body’s immune system (immunoablation) and replacing it with the patient’s own (autologous haemopoietic stem cell transplantation) innocent stem cells, a sort of immunological spring clean. Patients were randomly assigned to undergo transplantation (n=23) or just continue on best conventional treatment (n=22).

ASTIC was stimulated by reports which suggested that long-term regression of disease amounting to potential cure could be achieved. But the treatment is hazardous with major potentially lethal risks, so recruitment to the trial was cautious and only the most resistant cases were studied. And we used the most stringent criteria ever developed for the trial’s primary endpoint.

Medical Research: What are the main findings?

 Dr. Hawkey: In fact the criteria we used for success were so stringent (no symptoms, no signs of disease on total bowel examination and no need for treatment) that few patients achieved them. Nevertheless, there were improvements in the individual measures underlying this composite endpoint. Objective signs of disease disappeared so that the gut looked normal from mouth to anus in about a quarter of actively treated patients vs no controls. Eight vs two patients were adjudicated free of active disease on endoscopy and radiology at final assessment (p=0.054). Patients were able to come off drug treatments: by the end of a year 61% of HSCT patients off immunosuppressive drugs for >3 months vs 23% of controls (p=0.012). Ten vs two patients had lost symptoms of active disease, eight vs two for of them for > 3 months (p=0.052).

But treatment was challenging: there were 76 serious adverse events in HSCT patients (particularly infections) vs 38 in controls. One HSCT patient died.

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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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