Early Study Demonstrates Airways Can Be Transplanted from Aortic Templates

MedicalResearch.com Interview with:
Emmanuel Martinod MD PhD
Assistance Publique–Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny,
Université Paris Descartes, Fondation Alain Carpentier, Laboratoire de Recherche Bio-chirurgicale, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou
Paris, France 

MedicalResearch.com: What is the background for this exciting new technology and study? What are the main findings? 

Response: What is the background for this exciting new technology and study? What are the main findings?

Response:  The background is 10 years of research at laboratory followed by 10 years of academic clinical research.

We demonstrated the feasability of airway bioengeenring using stented aortic matrices for complex tracheal or bronchial reconstruction.  Continue reading

Optic Nerve Stroke: Bone Marrow Stem Cells Offer Hope of Vision Improvement

MedicalResearch.com Interview with:
Steven Levy MD

CEO, MD Stem Cells
Study Director, Stem Cell Treatment Studies

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

Response: MD Stem Cells is the sponsor of the Stem Cell Ophthalmology Treatment Study II (SCOTS 2) the largest stem cell study currently addressing retinal and optic nerve disease (NCT 03011541). SCOTS uses autologous bone marrow derived stem cells (BMSC) typically provided to the eyes by combining retrobulbar, subtenons and intravenous injections. Many retinal and optic nerve diseases are eligible including Retinitis Pigmentosa (RP), Age Related Macular Degeneration (AMD), Stargardts, Ushers, Glaucoma, Ischemic Optic Neuropathy, Optic Atrophy and others. Statistically significant improvements have been documented in key diseases and positive responses have been noted across most conditions treated. Mechanisms of action may include differentiation of the CD34 cells into neurons, secretion of neurotrophic factors, transfer of mitochondria and release of mRNA. These may benefit existing stressed cells as well as provide replacement of damaged or absent cells.

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Umbilical Cord Blood Stem Cells May Improve Symptoms in Children with Autism

MedicalResearch.com Interview with:

Michael G. Chez, M.D. Director of Pediatric Neurology Sutter Memorial Hospital Director of the Pediatric Epilepsy and Autism Programs Sutter Neuroscience Group 

Dr. Michael Chez

Michael G. Chez, M.D.
Director of Pediatric Neurology Sutter Memorial Hospital
Director of the Pediatric Epilepsy and Autism Programs
Sutter Neuroscience Group 

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

Response: The study looked at possible use of autologous cord blood as a source of stem cells in patients with autism. The patients had to have fairly good genetic screening per protocol and had confirmation of autism to participate.

The use of cord blood was a pilot cross over double blind study with hypothesis that a post natal factor or immune dysregulation may add to the autism clinical phenotype.

Cord blood ( the baby’s own from birth) is a safe source of mixed stem cell types and should be safe from rejection or autoimmune reaction in theory.

Infusion /placebo or placebo/infusion was randomized and observed and tested every 3 months with switch to other wing of treatment at 0 and 6 months. Total observation was over 1 year.

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Stem Cell Transplantation Offers Hope For Severe Scleroderma

MedicalResearch.com Interview with:

“Breastfeeding welcome here” by Newtown grafitti is licensed under CC BY 2.0

Picture of a female patient’s left arm, showing skin lesions caused by Scleroderma
Wikipedia image

Keith M. Sullivan, M.D.
James B. Wyngaarden Professor Of Medicine
Division of Cellular Therapy
Duke University Medical Center
Durham, North Carolina 27710, USA 

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

  • Scleroderma with internal organ involvement is a devastating  autoimmune disorder with considerable morbidity and high mortality which have not changed in 40 years of reporting. Effective new therapies are needed.
  • Despite 2 prior randomized trials showing benefit for reduced-intensity stem cell transplant vs. conventional cyclophosphamide immune suppression, clinical practice in the US did not change due in part due to concern about patient safety and durability of response (attached).
  • The current randomized trial compares 12 monthly infusions of cyclophosphamide with high-dose chemotherapy plus whole-body irradiation designed to wipe-out (myeloablate) the defective, self-reactive immune system and replace with the patients own stem cells which had been treated to remove self-reacting lymphocytes. This was the first study to test if myeloablative autologous could re-establish a normal functioning immune system in patients with scleroderma.

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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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Significant Amount of Medical Literature Contaminated With Misidentified Cells

MedicalResearch.com Interview with:

Serge Horbach MSc Institute for Science in Society Radboud University Nijmegen

Serge Horbach

Serge Horbach MSc
Institute for Science in Society
Radboud University Nijmegen
 

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

Response: Since the late 60s, researchers have pointed to issues in biomedical research stemming from the misidentification of cells. Starting with controversy around HeLa cells, researchers became aware of cells invading other cell cultures. Currently, 488 cell lines have become mixed up with the wrong cells, still often HeLa cells. This leads to errors in reporting research. For example, some research papers have reported results for “lung cancer cells” that turned out to be liver cancer cells, or even mouse cells.

We wanted to know what happened to past research and set out to estimate the number of scientific publications affected by misidentified cells. By tracing misidentified cells of the ICLAC database in Web of Science, we found 32.755 contaminated publications, or 0,8% of all literature in cell biology. These articles are cited by at least 500.000 other publications.

More worryingly, it turned out that this problem is highly stubborn. Currently, still a few dozen new articles are published every month reporting on other cells than were actually used, leading to a total of 1200 each year. And this number is not decreasing, in spite of a database of misidentified cells, of genetic testing availability, requirements by some prominent journals, or attention for the problem in the literature. We were also able to establish that this is not just a problem for newly emergent countries in the international research community, but also for countries with well-establishments research traditions. In spite of great efforts, the problem of cell misidentification is not at all solved.

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CMV Infections Increase Complications and Costs After Stem Cell Transplantation

MedicalResearch.com Interview with:

Dr. Jonathan Schelfhout, PhD Director, Outcomes Research Merck & Co. Inc. North Wales, PA

Dr. Schelfhout

Dr. Jonathan Schelfhout, PhD
Director, Outcomes Research
Merck & Co. Inc.
North Wales, PA

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

Response: The cost of hematopoietic stem cell transplantation has received increased attention after it was identified as a top 10 contributor to increasing healthcare costs in an AHRQ 2016 report. Many recent studies have explored the cost of HSCT but additional research is needed on the costly complications that can follow the transplant procedure. This research is particularly relevant for inpatient decision makers, as most transplant centers receive one bundled payment for the transplant and the treatment of any complications over the first 100 days.

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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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H. pylori May Increase Risk of Stomach Cancer By Turning On Subset of Stem Cells

MedicalResearch.com Interview with:
Michael Sigal PhD

Clinical scientist of the Charité — Universitätsmedizin Berlin
Investigator at the Max Planck Institute for Infection Biology 

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

Response: We have previously found that H. pylori can colonize gastric glands and that in colonized glands the epithelial turnover was increased. We wanted to characterize the mechanisms that control the gland turnover in the stomach.

We found that Axin2, a classic Wnt target gene, marks two different subpopulations of cells with stem cell properties, one of which is Lgr5-positive and the other one Lgr5-negative. Both populations are affected by Rspondin 3, that is produced in myofibroblasts right beneath the stem cell compartment. Rspondin is crucial for stem cell signaling and knockout of Rspondin 3 in myofibroblasts results in loss of Lgr5 and Axin2 expression. Once we increased the bioavailability of Rspondin, that now could also interact with cells outside of the stem cell compartment, we noticed that the number of Axin2 positive stem cells dramatically increased. Of interest, only Lgr5-negative cells expanded in number and proliferate more, while the Lgr5-positive cells remained silenced.

Infection with Helicobacter pylori leads to an expansion of Axin2-positive cells which is driven by increased expression of Rspondin3. Expansion of the long lived stem cell pool could be an explanation for how H. pylori infection increases the risk for gastric cancer.

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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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Unregulated Direct-to-Consumer Treatment Centers Provide Stem Cells for Patients With Heart Failure

MedicalResearch.com Interview with:

Dr. Paul J. Hauptman, MD Professor of Internal Medicine Division of Cardiology Assistant Dean, Clinical and Translational  Research Saint Louis University School of Medicine St. Louis MO 63110-0250

Dr. Hauptman

Dr. Paul J. Hauptman, MD
Professor of Internal Medicine
Division of Cardiology
Assistant Dean, Clinical and Translational  Research
Saint Louis University School of Medicine
St. Louis MO 63110-0250 

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

Response: A publication in 2016 by Leigh Turner from the University of Minnesota in 2016 shed light on the proliferation of stem cell centers or “businesses” that offer non FDA approved treatments, described as “stem cell therapy” for a variety of conditions. We opted to evaluate sites that claimed to treat heart failure. We collected data on type of infusion, need for a medical evaluation, board certification status of the center physician, cost and other factors. Self reported patient volumes were very variable. Most centers/businesses claimed to use autologous stem cells; a number offered ancillary treatment (i.e. vitamin infusions and hyperbaric oxygen); only one appeared to have a board-certified cardiologist involved. The costs were high for single infusions (mean price of $7694, SD 2737 for autologous cells; slightly less for allogeneic cells). Efficacy claims made during telephone calls with the centers were highly positive.

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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.

More Medical Research Interviews on MedicalResearch.com

Three Distinct Cardiac Stem Cell Populations Isolated from a Single Human Heart Biopsy

MedicalResearch.com Interview with:

Megan M. Monsanto, B.S. Joint Doctoral Student Department of Cell and Molecular Biology San Diego State University & University of California San Diego

Megan Monsanto

Megan M. Monsanto, B.S.
Joint Doctoral Student
Department of Cell and Molecular Biology
San Diego State University &
University of California San Diego

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

Response: In the field of cardiovascular research there is ongoing debate regarding the optimal cell population(s) to use for the treatment of patients with heart failure. A major reason being, the lack of understanding of the actions and synergism between distinct myocardial-derived stem cell populations. This prompted our group to establish a protocol to isolate multiple stem cell populations from a single human myocardial tissue sample that will allow for the discovery of new insights at the cellular level, with the ultimate goal being to achieve true myocardial regeneration upon injection back into the patient.

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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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