Author Interviews, Heart Disease, Stem Cells / 12.09.2016

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.
Author Interviews, Leukemia, NEJM, Transplantation / 08.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27654" align="alignleft" width="133"]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[/caption] 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.
Author Interviews, Emory, Gender Differences, Heart Disease, Stem Cells / 07.09.2016

[caption id="attachment_27692" align="alignleft" width="125"]MedicalResearch.com Interview with: Arshed A. Quyyumi MD; FRCP Dr. Arshed Auyyumi[/caption] 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.
Author Interviews, Diabetes, Heart Disease, Stem Cells / 30.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27474" align="alignleft" width="164"]Jolanta U Weaver, FRCP MRCS PhD CTLHE Dr. Jolanta Weaver[/caption] 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.
Author Interviews, Heart Disease, Stem Cells / 30.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27294" align="alignleft" width="125"]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[/caption] 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.
Author Interviews, Dermatology / 18.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27152" align="alignleft" width="200"]Thomas Bold President and CEO Communications at TrendLogic RenovaCare Inc. Thomas Bold[/caption] 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.
Author Interviews, Cancer Research, Stem Cells / 11.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26013" align="alignleft" width="160"]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[/caption] 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.
Author Interviews, Heart Disease, Stem Cells / 21.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25354" align="alignleft" width="160"]Fu Guosheng MD Professor and Chairman, Department of Cardiology Sir Run Run Shaw Hospital, College of Medicine Zhejiang University Hangzhou, China Dr. Fu Guosheng[/caption] 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.
Author Interviews, Heart Disease, Stem Cells / 11.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24225" align="alignleft" width="143"]Timothy D. Henry, MD, MSCAI Director, Division of Cardiology Cedars-Sinai Heart Institute Dr. Timothy Henry[/caption] 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.
Author Interviews, Science, Stem Cells / 29.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23919" align="alignleft" width="200"]Keir Menzies PhD Assistant Professor University of Ottawa Brain and Mind Research Institute University of Ottawa Dr. Keir Menzies[/caption] 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.
Author Interviews, Dermatology, PLoS, Stem Cells / 06.04.2016

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.
Author Interviews, Johns Hopkins, PLoS, Stem Cells / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22010" align="alignleft" width="133"]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[/caption] 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.
Author Interviews, Cancer Research, Radiation Therapy, Stem Cells / 11.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21484" align="alignleft" width="120"]Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714 Dr. Erina Vlashi[/caption] 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. 
ALS, Alzheimer's - Dementia, Author Interviews, JAMA, Multiple Sclerosis, Neurological Disorders, Stem Cells / 12.01.2016

[caption id="attachment_20586" align="alignleft" width="200"]Prof. Dimitrios Karussis M.D., Ph.D. Professor of Neurology Head, Multiple Sclerosis Center Hadassah BrainLabs Prof. Dimitrios Karussis[/caption] MedicalResearch.com Interview with: Prof. Dimitrios 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.
Author Interviews, Breast Cancer, Stem Cells / 29.12.2015

[caption id="attachment_20336" align="alignleft" width="200"]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[/caption] 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.
Author Interviews, Hepatitis - Liver Disease, Nature / 01.12.2015

[caption id="attachment_19732" align="alignleft" width="125"]Prof. Yaakov Nahmias Director of the Alexander Grass Center for Bioengineering Hebrew University of Jerusalem Dr. Nahmias[/caption] 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.
Author Interviews, Kidney Disease, Nature / 27.10.2015

[caption id="attachment_18851" align="alignleft" width="100"]Daniele Zink PhD Institute of Bioengineering and Nanotechnology Singapore Dr. Zink[/caption] 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 1, 2. 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 1, 2 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.
Author Interviews, Genetic Research, Kidney Disease, Nature, Stem Cells / 24.10.2015

[caption id="attachment_18772" align="alignleft" width="140"]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[/caption] 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.
Author Interviews, Pancreatic, Stem Cells / 14.09.2015

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.
Author Interviews, Duke, HPV, Stem Cells / 01.04.2015

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.
Author Interviews, Stem Cells / 26.02.2015

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?
Author Interviews, Dermatology, PLoS, Stem Cells / 29.01.2015

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.
Author Interviews, Stem Cells / 31.12.2014

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.
Heart Disease, Kidney Disease, Stem Cells / 20.12.2014

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.
Author Interviews, Dermatology, JAMA, NIH, Transplantation / 11.09.2014

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.
Author Interviews, Heart Disease, Stem Cells / 21.08.2014

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.