People with a certain gene have an adverse reaction to the antiretroviral efavirenz

Liz HighleymanCorrespondent An HIV-positive bone marrow transplant recipient at the Mayo Clinic experienced prolonged viral remission lasting nearly 10 months longer than the so-called Boston patients after interrupting antiretroviral therapy (ART), according to a report at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) last month in Seattle.

Although his viral load eventually rebounded, his HIV reservoirs appeared to be reduced.

The only person known to be cured of HIV Timothy Ray Brown, known as the Berlin Patient stopped ART when he received a bone marrow transplant to treat leukaemia and has not had detectable virus for 10 years. Brown received a transplant from a donor with a double CCR5-delta-32 mutation, meaning they lack the CCR5 co-receptors most types of HIV use to enter T-cells.

It is unclear whether his sustained remission is attributable to the donors CCR5 mutation, the strong chemotherapy conditioning regimen used to kill off cancerous blood cells, a graft-versus-host reaction or multiple factors.

Bone marrow transplantation is apparently not sufficient to eradicate HIV.

A few years ago, Timothy Henrich reported on two HIV-positive bone marrow transplant patients in Boston who got stem cells from wild-type donors without the CCR5-delta-32 mutation, received a milder conditioning regimen and experienced acute graft-versus-host disease (GVHD). Both men maintained undetectable viral load longer than expected after interrupting ART, but eventually they experienced viral rebound at three and eight months after stopping HIV treatment.

The latest case, presented by Nathan Cummins of the Mayo Clinic in Rochester, Minnesota, and colleagues, involved a 55-year-old man who was diagnosed with HIV in 1990 and started combination ART in 1999 with a CD4 T-cell count of 300 cells/mm3. He stopped treatment between 2004 and 2009 for unexplained reasons, then restarted ART consisting of ritonavir-boosted atazanavir (Prezista) plus tenofovir disoproxil fumarate (DF) and emtricitabine (the drugs in Truvada).

In April 2013 the man was diagnosed with B-cell acute lymphoblastic leukaemia.

In anticipation of chemotherapy, his ART regimen was switched to raltegravir (Isentress), etravirine (Intelence), and tenofovir DF/emtricitabine. In October 2013 he underwent reduced intensity conditioning followed by an allogeneic stem cell transplant from a CCR5 wild-type donor.

At the time of transplantation the man had an HIV viral load of 25 copies/ml and a CD4 count of 288 cells/mm3, and he stayed on ART without interruption. After the transplant he developed opportunistic infections (E. coli septicaemia and pneumocystis pneumonia) and experienced GVHD at four months post-transplant.

The man continued on ART for more than two years after transplantation, mostly with detectable plasma viral load levels. HIV RNA was also undetectable in gut biopsy samples. HIV DNA in his peripheral blood cells became undetectable by day 56, and repeated leukapheresis procedures showed significant reductions in HIV RNA and DNA reservoir size.

In addition, that mans HIV antibody levels decreased, as indicated by weaker Western blot bands. However, single genome sequencing and phylogenetic analysis identified identical HIV clones at day 142, possibly due to homoeostatic proliferation, or replication of latently infected cells, while he had GVHD.

After having such low HIV levels for a prolonged period, the man underwent an analytic treatment interruption, or carefully monitored discontinuation of ART. His plasma HIV RNA levels were tested every two weeks for the first 12 weeks of ART interruption, then every four weeks.

At day 288 9,6 months after stopping ART he was found to have low-level viral rebound to 60 copies/ml. This rose to 1640 copies/ml by day 293, requiring that he restart HIV treatment.

The man had no evidence of drug resistance and his viral load was re-suppressed within a month.

Allogeneic peripheral blood stem cell transplantation in the setting of HIV is associated with significant reductions in HIV reservoir size by multiple measures, including prolonged combination ART-free remission, the researchers concluded.

They added that stem cell transplantation in the setting of suppressed viral replication may be associated with loss of HIV-specific immunity, and hypothesised that immune activation in the setting of GVHD without anti-HIV specific immunity may cause homoeostatic proliferation of latently infected cells, decreasing the chance of HIV eradication. http://www.aidsmap.com.

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Researchers report positive bone marrow transplant case - The Herald

Rich Garton, CTV Windsor Published Tuesday, March 7, 2017 9:15AM EST Last Updated Tuesday, March 7, 2017 3:50PM EST

A Windsor infant with a rare genetic disorder has found a bone marrow match.

CTV Windsor first brought you Madalayna Ducharme's story a few months ago -- when her parents, Tamara and Charles made a plea for people to become bone marrow and stem cell donors.

It was on the heels of them learning Madalayna suffers from a rare genetic disorder called malignant infantile osteopetrosis. The side effects cause progressive vision and hearing loss, bone density and could potentially be fatal.

Doctors contacted the family this week and Ducharme is already undergoing treatment and is being prepped for the bone marrow transplant.

CTV News spoke with the family -- and they are elated with the news, but the Ducharme's excitement is tempered by a fear of what lies ahead.

We're a little scared at the same time because of the stuff she has to go through, says Tamara Ducharme. She has a regiment she has to go through before she can get this transplant.

That includes heavy doses of chemotherapy, with potential side effects, before a bone marrow transplant can take place.

Chemo is not going to be pretty, says Tamara Ducharme. She's a happy little girl, she cries once in a while like a regular child, she's going to be very ill and I don't know if I'm ready for that."

For now, they will borrow strength from their warrior princess.

Tamara Ducharme took to Facebook this morning to provide the good news. "We are sending big THANKS to all who have supported us, got swabbed, volunteered and donated blood," she posted.

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Windsor infant "warrior princess" finds a bone marrow match - CTV News

Globalnews.ca

Could you save his life? Edmonton boy needs to find stem cell match Globalnews.ca Doctors say he needs a bone marrow transplant. Now, the family is desperately searching for a stem cell match. The world needs to know that this is what we need and this can save kids' lives, Mishio said. Not just Brady's life there's other ...

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Could you save his life? Edmonton boy needs to find stem cell match - Globalnews.ca

Dr. Kenneth Pettine, a board certified retired Orthopedic Surgeon and one of the Top 50 Spine Surgeons and Specialist to Know according to Becker's Spine Review, is offering to educate the public about mesenchymal stem cell therapy in Northern Colorado. Mesenchymal stem cells are being studied by Dr. Pettine for their ability to treat orthopedic conditions such as osteoarthritis and other joint and disc related chronic neck and back pain.

(PRWEB) March 07, 2017

Dr. Kenneth Pettine, a Northern Colorado board-certified retired orthopedic surgeon, is currently researching the use of the mesenchymal stem cell and their potential in treating orthopedic conditions such as osteoarthritis or other joint and disc related issues. He's now releasing more information about what these incredible stem cells are and the exciting therapeutic opportunities of mesenchymal stem cell therapy for the interested public in Northern Colorado.

Stem cells are rare, unique cells in our body that can duplicate themselves over and over again and can continue to regenerate throughout our lives. Each particular stem cell can only become either one type or a very limited number of cell types. As we get older, we have fewer stem cells in our body, which is why we have a decreased ability to heal and avoid diseases like cancer. Introducing new stem cells to the body could help counteract the effects of degenerated joints and chronic neck and back pain.

Mesenchymal stem cell are one type of stem cell, and the one that Dr. Pettine is using to focus his clinical research on stem cell therapy. This particular type of stem cell modulates your immune system, is extremely anti-inflammatory and has many positive effects in helping your body treat autoimmune conditions. The mesenchymal stem cell is the main cell helping your body heal from orthopedic and spine injuries and helping treat degenerative conditions such as arthritis.

Almost all of this research involves mesenchymal stem cells obtained from bone marrow. Most all these studies involved obtaining the mesenchymal stem cell from a donor's bone marrow and then expanding these cells in a laboratory. The number of mesenchymal stem cells in a petri dish can be increased to result in several hundred million cells. These cells are then put into recipient animals and humans to study their ability to treat numerous autoimmune diseases such as Parkinson's, multiple sclerosis, crohn's disease, asthma, lupus, to name just a few. These cells are also being studied to treat and regrow damaged heart muscle after a heart attack. Extensive research is being conducted to evaluate the safety and efficacy of utilizing mesenchymal stem cells to treat orthopedic conditions such as osteoarthritis of your joints and disc related chronic back and neck pain.

This has exciting implications for chronic neck and back pain sufferers. These Mesenchymal stem cells could help regenerate tissue in the spine, reversing issues like degenerative disc disease. The stem cells could also decrease pain-causing inflammation and help patients recover from accidents and injuries faster.

If you are a chronic neck or back pain sufferer and would like to learn more about Dr. Pettine's research on Mesenchymal stem cell therapy, visit his website at http://www.KennethPettine.com for more information.

About Dr. Kenneth Pettine Dr. Pettine is currently the principal investigator for 18 FDA studies evaluating non-fusion spine surgery implants and stem cells for their uses in treating spine pathology. He is considered a pioneer in the field of biologics to treat orthopedic and spine pathology. He founded The Rocky Mountain Associates in Orthopedic Medicine in 1991 to offer patients a non-fusion surgical option for their neck and back pain. He co-invented the FDA-approved Prestige cervical artificial disc and the Maverick Artificial Disc. He is currently focused on educating anyone interested in learning about the use of Mesenchymal stem cell therapy. You can learn more about stem cells and Dr. Pettine at his website, http://www.KennethPettine.com.

For the original version on PRWeb visit: http://www.prweb.com/releases/2017/03/prweb14124517.htm

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Northern Colorado Doctor Kenneth Pettine Releases Information on Mesenchymal Stem Cell Therapy for Chronic Neck ... - Benzinga

The skin cells of four adults with schizophrenia have provided an unprecedented window into how the disease began while they were still in the womb, according to a recent paper in Schizophrenia Research.

The paper was publishedby researchers at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo in collaboration with the Icahn School of Medicine at Mount Sinai. It provides what the authors call the first proof of concept for their hypothesis that a common genomic pathway lies at the root of schizophrenia.

The researchers say the work is a first step toward the design of treatments that could be administered to pregnant mothers at high risk for bearing a child with schizophrenia, potentially preventing the disease before it begins.

The authors gained insight into the early brain pathology of schizophrenia by using skin cells from four adults with schizophrenia and four adults without the disease that were reprogrammed back into induced pluripotent stem cells and then into neuronal progenitor cells.

The next step in the research is to use these induced pluripotent stem cells to further study how the genome becomes dysregulated, allowing the disease to develop.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post: Faulty genomic pathway linked to schizophrenia developing in utero, study finds

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Skin cells of schizophrenia patients reveal faulty genetic pathway that began in womb - Genetic Literacy Project

MILPITAS, Calif.--(BUSINESS WIRE)--Applied StemCell (ASC), a leading stem cell and genome-editing company with a goal to advance genome editing and stem cell technologies for biomedical research and clinical applications, welcomes Dr. Michele Calos as a member of the companys Scientific Advisory Board (SAB).

Dr. Michele Calos is a Professor of Genetics at the Stanford University School of Medicine, Vice President of the American Society of Gene and Cell Therapy, and has served as an Advisory Committee member for the US FDA, grant review panels for the NIH and NSF, and on numerous editorial review committees of scientific journals. She is a leader in the field of molecular genetics and has developed several novel vector systems for genetic manipulation of mammalian cells. In particular, she developed novel methods for sequence-specific integration in mammalian cells using the C31 phage integrase system. A similar integrase system was also successfully used in site-specific integration in human ES and iPS cells. For this work, Dr. Calos holds a joint patent application with Applied StemCells Chief Scientific Officer, Dr. Ruby Yanru Chen-Tsai and several other Stanford researchers. Dr. Calos pioneering work with C31 integrase also set the scientific stage for ASCs TARGATT integrase technology, which was co-developed by Dr. Chen-Tsai and Dr. Liqun Luo of Stanford University for gene modification in mouse models.

We are extremely pleased to have Dr. Calos join as a member of our scientific advisory board. With her impressive background in integrase gene modification technology and gene therapy, Dr. Calos will be an invaluable guide in furthering expansion of our genome editing platforms and our gene/cell therapy pipeline, said Ruby Yanru Chen-Tsai, Ph.D., Co-founder and Chief Scientific Officer of Applied StemCell.

Dr. Calos and her research team are currently focused on gene therapy and genome engineering for the treatment of Duchenne and Limb Girdle Muscular Dystrophies and developing further novel strategies for gene and cell therapy.

About Applied StemCell, Inc.

Applied StemCell, Inc. is a leading stem cell and gene-editing company focused on the development of products and therapeutics that are enabled by its proprietary gene editing platform technologies TARGATT and CRISPR/Cas9. For more information, please visit http://www.appliedstemcell.com.

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Applied StemCell Announces the Appointment of Dr. Michele Calos, Stanford Professor and Vice President of the ... - Business Wire (press release)

An HIV-positive bone marrow transplant recipient at the Mayo Clinic experienced prolonged viral remission lasting nearly 10 months longer than the so-called Boston patients after interrupting antiretroviral therapy (ART), according to a report at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) last month in Seattle. Although his viral load eventually rebounded, his HIV reservoirs appeared to be reduced.

The only person known to be cured of HIV Timothy Ray Brown, known as the 'Berlin Patient' stopped ART when he received a bone marrow transplant to treat leukaemia and has not had detectable virus for ten years. Brown received a transplant from a donor with a double CCR5-delta-32 mutation, meaning they lack the CCR5 co-receptors most types of HIV use to enter T-cells. It is unclear whether his sustained remission is attributable to the donor's CCR5 mutation, the strong chemotherapy conditioning regimen used to kill off cancerous blood cells, a graft-versus-host reaction or multiple factors.

Bone marrow transplantation is apparently not sufficient to eradicate HIV. A few years ago, Timothy Henrich reported on two HIV-positive bone marrow transplant patients in Boston who got stem cells from 'wild-type' donors without the CCR5-delta-32 mutation, received a milder conditioning regimen and experienced acute graft-versus-host disease (GVHD). Both men maintained undetectable viral load longer than expected after interrupting ART, but eventually they experienced viral rebound at three and eight months after stopping HIV treatment.

The latest case, presented by Nathan Cummins of the Mayo Clinic in Rochester, Minnesota, and colleagues, involved a 55-year-old man who was diagnosed with HIV in 1990 and started combination ART in 1999 with a CD4 T-cell count of 300 cells/mm3. He stopped treatment between 2004 and 2009 for unexplained reasons, then restarted ART consisting of ritonavir-boosted atazanavir (Prezista) plus tenofovir disoproxil fumarate (DF) and emtricitabine (the drugs in Truvada).

In April 2013 the man was diagnosed with B-cell acute lymphoblastic leukaemia. In anticipation of chemotherapy, his ART regimen was switched to raltegravir (Isentress), etravirine (Intelence), and tenofovir DF/emtricitabine. In October 2013 he underwent reduced intensity conditioning followed by an allogeneic stem cell transplant from a CCR5 'wild-type' donor.

At the time of transplantation the man had an HIV viral load of 25 copies/ml and a CD4 count of 288 cells/mm3, and he stayed on ART without interruption. After the transplant he developed opportunistic infections (E. coli septicaemia and pneumocystis pneumonia) and experienced GVHD at four months post-transplant.

The man continued on ART for more than two years after transplantation, mostly with detectable plasma viral load levels. HIV RNA was also undetectable in gut biopsy samples. HIV DNA in his peripheral blood cells became undetectable by day 56, and repeated leukapheresis procedures showed significant reductions in HIV RNA and DNA reservoir size.

In addition, that man's HIV antibody levels decreased, as indicated by weaker Western blot bands. However, single genome sequencing and phylogenetic analysis identified identical HIV clones at day 142, possibly due to homeostatic proliferation, or replication of latently infected cells, while he had GVHD.

After having such low HIV levels for a prolonged period, the man underwent an analytic treatment interruption, or carefully monitored discontinuation of ART. His plasma HIV RNA levels were tested every two weeks for the first 12 weeks of ART interruption, then every four weeks.

At day 288 9.6 months after stopping ART he was found to have low-level viral rebound to 60 copies/ml. This rose to 1640 copies/ml by day 293, requiring that he restart HIV treatment. The man had no evidence of drug resistance and his viral load was re-suppressed within a month.

"Allogeneic peripheral blood stem cell transplantation in the setting of HIV is associated with significant reductions in HIV reservoir size by multiple measures, including prolonged combination ART-free remission," the researchers concluded.

They added that stem cell transplantation in the setting of suppressed viral replication may be associated with loss of HIV-specific immunity, and hypothesised that "immune activation in the setting of GVHD without anti-HIV specific immunity may cause homeostatic proliferation of latently infected cells, decreasing the chance of HIV eradication."

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Researchers report case of bone marrow transplant patient off ART for 288 days without HIV rebound - aidsmap

FOX31 Denver

Sickle cell anemia patient 'cured' by gene therapy, doctors say FOX31 Denver Essentially, researchers extracted bone marrow from the patient, harvested the stem cells and altered the genetic instructions so that they would make normal hemoglobin. Next, they treated the patient with chemotherapy for four days to eliminate his ... Gene therapy shows early promise against sickle cellChicago Tribune Doctors Claim They've Cured a Boy of a Painful Blood Disorder ...Futurism Will Sickle Cell Be the Next Disease Genetic Engineering Cures?Gizmodo Ligue 1 Talk -IFLScience all 65 news articles »

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Sickle cell anemia patient 'cured' by gene therapy, doctors say - FOX31 Denver

International Stem Cell Corporation Announces Third Patient with Parkinson's Disease in Phase I Clinical Trial P&T Community 28, 2017 (GLOBE NEWSWIRE) -- International Stem Cell Corporation (OTCQB:ISCO), a California-based clinical stage biotechnology company developing stem cell-based therapies and biomedical products, today announced the third patient in the clinical trial ... and more »

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International Stem Cell Corporation Announces Third Patient with Parkinson's Disease in Phase I Clinical Trial - P&T Community

"Stem cells have enormous potential for alleviating suffering for many diseases which currently have no effective therapy. The field has progressed to the clinic and it is important that this pathway is underpinned by excellent science and rigorous standards of clinical research. The journal provides an important avenue of publication in translational aspects of stem cell therapy spanning preclinical studies, clinical research and commercialization."

Timothy O'Brien,Editor-in-Chief,Stem Cell Research & Therapy

"The study of stem cells is one of the most exciting areas of contemporary biomedical research. We believe that Stem Cell Research & Therapy will act as a highly active forum for both basic and translational research into stem cell biology and therapies. Specifically, by developing this forum for cutting edge research, we hope that Stem Cell Research & Therapy will play a significant role in bringing together the critical information to synergize stem cell science with stem cell therapies."

Rocky S Tuan,Editor-in-Chief,Stem Cell Research & Therapy

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Stem Cell Research & Therapy | Home page

A U.S. biotech company is preparing to start experiments using stem cells to try to stimulate 20 brain-dead patients back to life. And no, this isn't an elevator pitch for a sci-fi horror film.

The Mind Unleashed reports the company Bioquark will be trying to use stem cells to regrow and stimulate neurons to bring the patients back from brain death. It works like this: They implant stem cells in the patient's brain while also infusing the spinal cord with chemicals typically used to try and wake up coma patients. Then, hopefully, brain activity is essentially 'jump-started.' The technique is untested, so these experiments will go a long way toward proving (or disproving) the viability of the process.

Bioquark CEO Ira Pastor said they hope to see some results within 2-3 months after treatment begins, with the long-term goal being to develop techniques for brain-dead patients to eventually be able to make a full recovery. Which is certainly a heady, and ethically tricky, goal. You know, and also kind of scary. Ambitious and potentially live-saving, but still a little freaky.

What do you think of the technique? Is this going to revolutionize brain recovery or be the first step toward the T-virus?

(via The Mind Unleashed)

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Scientists moving ahead with research to resurrect the dead with stem cells - Blastr

LONDON Technavio analysts forecast the global stem cell therapy market to grow at a compound annual growth rate of close to 37 percent during the forecast period, according to their latest report.

The research study covers the present scenario and growth prospects of the global stem cell therapy market for 2017-2021. To determine the market size, the study considers revenue generated from allogenic and autogenic stem cell therapies.

The Americas are the largest regional segment of the global stem cell therapy market, responsible for generating over 56 percent of the total revenue (2016 figures). The region is expected to continue market dominance through the forecast period, driven by increasing demand for stem cell therapy products and investments into R&D.

Technavio analysts highlight the following factors as contributing to the growth of the global stem cell therapy market:

Increase in federal funding in stem cell therapy.

Sapna Jha, one of the lead research analysts at Technavio for medical imaging research, says, Many stem cell research institutes and small companies are involved in cutting-edge R&D and are yielding encouraging results. These institutions are witnessing an increased flow of investments from federal organizations, due to the realization of the importance of regenerative medicine.

The U.S. National Institutes of Health, a major funding government organization invested approximately USD 1.5 billion in stem cell research projects in 2016. Similarly, several state-level organizations such as California Institute for Regenerative Medicine has contributed USD 3 billion to stem cell research in 2014. Such funding will help various research institutes to discover and develop regenerative medicines, which will boost the global regenerative medicine market enormously.

Growing demand for personalized medicine.

The health care sector is creating a high demand for personalized medicine, which could offer game-changing opportunities for the vendors. These medicines offer treatments based on the individual characteristics, needs, and preferences, which will vastly improve the quality of health care. Individuals are increasingly banking their stem cells for future treatments. Research organizations are also extensively exploring ways to develop personalized treatments with stem cells, which could eventually erase the conventional medicine system and help in the effective treatment of various diseases such as diabetes and cancer.

Demand for development of effective drugs for cardiology and degenerative disorders.

There has been an increased demand to develop effective drugs for cardiology and degenerative disorders, for which there were no effective treatment plans before the advent of stem therapies. The discovery of possible cardiac stem cells uncovered new arenas to repair hearts injured due to acute myocardial infarction or coronary artery disease, says Sapna.

Researchers are studying and developing approximately 19 product candidates for the treatment of cardiac disorders, with eight of them in Phase III, and six in Phase II.

Technavio is a global technology research and advisory company. This report was made available through The Associated Press.

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Opinion/Commentary: Global stem cell therapy market to showcase growth - The Daily Progress

Almost 30 years ago, the federal government helped make it easier for patients with leukemia and lymphoma to receive lifesaving stem cell transplants. Now, we need the federal governments help again to ensure that Medicare patients with these cancers and other serious blood disorders can access the care they need.

In 1987, Congress approved funding for a national database of patients willing to donate bone marrow or peripheral blood stem cells. That database is now known as the Be The Match Registry, operated by the National Marrow Donor Program/Be The Match. According to the NMDP/Be The Match, patients searching the registry have access to 27 million potential volunteer bone marrow and peripheral blood stem cell donors worldwide, along with more than 680,000 units of cord blood donated by mothers after giving birth.

Having access to such a large registry has made it easier for patients to find a match if they dont have a fully matched sibling donor, which is the case for about 70 percent of patients who receive a stem cell transplant. The registry has helped 80,000 patients receive bone marrow transplants, peripheral blood stem cell transplants, or cord blood transplants from an unrelated donor.

While the federal governments foresight and financial support have helped make adult stem cell and cord blood transplants the only cure available for these diseases possible for thousands of patients, Medicare coverage policies have not kept pace with this breakthrough treatment.

Medicare is more restrictive than private insurance companies in deciding for what indications stem cell transplants and cord blood transplants will be covered. With private insurance companies, we have the opportunity to talk with a medical director about the indication and provide literature to support the decision for a transplant. This opportunity is not available for our Medicare patients.

In most cases, Medicare doesnt decide whether to cover a stem cell or cord blood transplant until after the procedure is completed. This leaves most Medicare patients an impossible choice: Turn down their only chance at a cure or potentially face paying the significant cost of a transplant themselves. Even when Medicare does decide to reimburse for these transplants, according to the NMDP/Be The Match, it covers less than half the cost of the transplant.

Addressing this issue is especially important because seniors make up a large portion of the patients with the cancers and blood diseases that can be cured by a stem cell or cord blood transplant. For example, 24 of the 65 patients who received stem cell or cord blood transplants at University of Virginia Health System in 2016 had Medicare coverage.

So I am asking the Centers for Medicare & Medicaid Services to expand Medicare coverage for stem cell and cord blood transplants, along with paying for the search and procurement costs as they already do for solid organ transplants.

The federal government has helped save the lives of tens of thousands of patients through better access to stem cell and cord blood transplants. I hope now they will act to make sure all Medicare patients who need one of these transplants can receive it.

Tamila L. Kindwall-Keller, DO, MS is the associate clinical director of the Stem Cell Transplant Program at the University of Virginia Health System.

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Opinion/Commentary: Seniors put at risk by outdated Medicare policies - The Daily Progress

The Harvard Stem Cell Institute is developing new techniques to grow and transplant heart cells, replacing those lost to cardiovascular disease.

The greatest threat to the long-term health and well-being of people living with diabetes is cardiovascular disease. The diabetic population as a whole is two to four times more likely than non-diabetics to develop heart disease or suffer a stroke. Type 1 diabetes, which is most often diagnosed in childhood and adolescence, is particularly devastating, as one New England Journal of Medicine study associated it with a ten-fold increase in cardiovascular disease.

The human adult heart has about five billion heart cells, all pulsing as a coordinated orchestra with every heartbeat. These cells can be killed by high blood pressure, blood clots, heart attacks, and other byproducts of cardiovascular disease. The heart has an age-related block in its ability to make new heart cells, so that damaged cells are not replaced in the latter half of life, precisely when we need them the most. A typical patient with heart failure has lost over a billion heart cells.

Harvard Stem Cell Institute (HSCI) investigators are developing ways to make replacement heart cells and provide them with the right cues so that the new cells play as needed in the orchestra.

Both embryonic stem cells and induced pluripotent stem cells mature cells that are manipulated back to a stem cell state can be harnessed to create new heart cells. The difficulty is that the heart cells made with stem cells resemble the heart cells of an infant, rather than adult heart cells. To function in adult hearts, the new heart cells must mature and then be able to survive within the constantly beating environment of the heart.

The scientific community has generated the technology to make heart cells that are immature, but very few heart cells derived from stem cells integrate into the normal heart tissue as mature heart cells. At the HSCI, our researchers are focused on understanding how to take these new heart cells all the way to maturity and stability, so they can be used as an effective therapy.

HSCI scientists are also developing ways of using the bodys heart matrix the rich, intricate scaffold of the heart that serves as the permanent home for our heart cells to guide maturation and prolong the survival of heart cells derived from stem cells after implantation.

The heart matrix is like the sheet music for the heart orchestra. It tells the heart cells where to sit and how to function with their neighbors so that a heartbeat is in sync. The problem of redrawing these matrix-directed instructions from scratch once seemed too daunting to tackle.

By breaking down the hearts scaffold material into thousands of individual chemicals, HSCI researchers hope to rebuild the environments that allow immature heart cells to mature. Armed with this knowledge, it will be possible to construct real adult heart tissue in the laboratory, as well as realistic approaches to transplanting patient-specific heart cells into their damaged organs.

In addition to these ambitious projects, HSCI is pursuing interim objectives before reaching the ultimate goal of reconstructing the heart. For example, a recent study led to the identification of a blood circulating factor that declines with age but, when injected, can reverse age-related heart enlargement and accompanying heart failure. If this is successful in human studies, we will have identified a new therapeutic approach for the aging heart.

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Heart Disease | Harvard Stem Cell Institute (HSCI)

Recent advancements in stem cells research have given hope for successfully treating diabetic heart disease (DHD), renowned New Zealand-based researcher in cardiovascular diseases Dr Rajesh Katare said on Tuesday.

DHD affected the muscular tissues of the heart leading to complications and it had been demonstrated that resident stem cells of myocardium can be stimulated to repair and replace e degenerated cardiac myocytes resulting in a novel therapeutic effect and ultimately cardiac regeneration, he said.

Katare, Director of Cardiovascular Research Division in the University of Otago, New Zealand, was delivering the keynote address at the continuing medical education programme on "Role of Micro-RNAs and stem cells in cardiac regeneration in diabetic heart disease" at the Karaikal campus of premier health institute JIPMER.

Presenting clinical evidences, Katare said stem cell therapy certainly presented a new hope for successfully treating DHD.

Jawaharlal Institute of Post Graduate Medical Education (JIPMER) Director Dr Subash Chandra Parija pointed out that it was the first such programme on the role of stem cells in cardiac regeneration in the whole of the country.

He said as diabetes was highly prevalent in the country, providing treatment for DHD had become a big challenge. Patients suffering from the condition have to undergo lifelong treatment and medications. "In this backdrop, advancements in stem cell therapy assume significance," he said. (REOPENS MES10)

Parija also said the government general hospital in

Karaikal being currently used by JIPMER for clinical teaching of students would have upgraded facilities.

He said a new building for the college would be constructed at a cost of Rs 497.10 crore soon.

The proposed up-gradation of the GH having 506 beds would help in imparting advanced clinical teaching and effective exposure of the medicos to various nuances of the diagnosis.

The Director also said JIPMER (Karaikal) had drawn up special post-graduate and fellowship programmes including on family medicine, tropical medicine, trauma care and cancer management.

Originally posted here:
Stem cell therapy can help in treating diabetic heart disease - Business Standard

An Edmonton police officer is counting on the city he serves to help save his sons life.

Brady Mishio, 8, has an aggressive form of leukemia and needs a bone marrow transplant. His dad Terry desperately hopes someone who is a match will hear his plea.

Bradys family received the news of his illness in November after they took him for treatment of a persistent fever and flu.

You become that family that's searching for hope and have all these dreams and things for your children, and then one day, one day it's taken away from you so quickly, said Mishio.

The diagnosis was a form of cancer that starts in blood stem cells called acute myelogenous leukemia (AML). It is the most common leukemia found in adults but is less common in children. Brady began chemotherapy right away.

Four days into chemo he had a reaction to some of the drugs that they were giving him and he quit breathing and had a seizure, said Mishio, a 20-year veteran of the Edmonton Police Service who was once forced off work for a year with a brain injury after being kicked while making an arrest.

Bradys doctors found a drug combination that worked and the boy just finished his third round of treatment. He is in an isolation unit in hospital and the next step is a bone marrow transplant.

It gives Brady a second chance at life, at cleaning out his bone marrow and hopefully eliminating the cancer, said his father, while fighting tears.

Bradys family is not a match and Mishio is reaching out publicly, hoping he can help his child by finding a suitable donor. The test is a simple mouth swab. Donors must be between 17 and 35 and be in relatively good health, says Robyn Henwood, a stem cell territory manager for Canadian Blood Services. Younger people have fewer antibodies in their blood, lowering the risk of rejection.

Once registered, potential donors stay in the agencys registry until they are 60 years old.

Less than 25 per cent of patients find a bone marrow match in their own family, says Henwood.

So every single person we add to our database is giving hope to those who are looking for a match or who are likely going to die if we don't find them one.

In most cases, the process to donate bone marrow is much like giving blood and takes four to six hours to complete.

A clinic is being held Thursday, March 9 from 4 p.m. to 8 p.m. at Holy Cross Ukrainian Catholic Church. Interested donors who cant make that clinic can be tested at the Canadian Blood Services clinic next to University Hospital or register at blood.ca to be mailed a swab kit.

Mishio is amazed by the bravery of his son through this battle.

He's a fighter and there's many days where he'll be rubbing my back and kind of telling me it's going to be OK, and that's when I'm like, 'I got to be strong for him.'

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Edmonton police officer appeals for bone marrow donor to save 8 ... - CTV News

Researchers are reporting early success using gene therapy to treat, or even potentially cure, sickle cell anemia.

The findings come from just one patient, a teenage boy in France. But more than 15 months after receiving the treatment, he remained free of symptoms and his usual medications.

That's a big change from his situation before the gene therapy, according to his doctors at Necker Children's Hospital in Paris.

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For years, the boy had been suffering bouts of severe pain, as well as other sickle cell complications that affected his lungs, bones and spleen.

Medical experts stressed, however, that much more research lies ahead before gene therapy can become an option for sickle cell anemia.

It's not clear how long the benefits will last, they said. And the approach obviously has to be tested in more patients.

"This is not right around the corner," said Dr. George Buchanan, a professor emeritus of pediatrics at the University of Texas Southwestern Medical Center in Dallas.

That said, Buchanan called the results a "breakthrough" against a disease that can be debilitating and difficult to treat.

Buchanan, who wasn't involved in the research, helped craft the current treatment guidelines for sickle cell.

"This is what people have been wanting and waiting for," he said. "So it's exciting."

Sickle cell anemia is an inherited disease that mainly affects people of African, South American or Mediterranean descent. In the U.S., about 1 in 365 black children is born with the condition, according to the U.S. National Heart, Lung, and Blood Institute.

It arises when a person inherits two copies of an abnormal hemoglobin gene one from each parent. Hemoglobin is an oxygen-carrying protein in the body's red blood cells.

When red blood cells contain "sickle" hemoglobin, they become crescent-shaped, rather than disc-shaped. Those abnormal cells tend to be sticky and can block blood flow causing symptoms such pain, fatigue and shortness of breath. Over time, the disease can damage organs throughout the body.

There are treatments for sickle cell, such as some cancer drugs, Buchanan pointed out, but they can be difficult to manage and have side effects.

There is one potential cure for sickle cell, Buchanan said: a bone marrow transplant. In that procedure, doctors use chemotherapy drugs to wipe out the patient's existing bone marrow stem cells which are producing the faulty red blood cells. They are then replaced with bone marrow cells from a healthy donor.

A major problem, Buchanan said, is that the donor typically has to be a sibling who is genetically compatible and free of sickle cell disease.

"We've known for a long time that bone marrow transplants can work," Buchanan said. "But most patients don't have a donor."

That's where gene therapy could fit in. Essentially, the aim is to genetically alter patients' own blood stem cells so they don't produce abnormal hemoglobin.

In this case, the French team led by Dr. Marina Cavazzana focused on a gene called beta globin. In sickle cell anemia, beta globin is mutated.

First, the researchers extracted a stem cell supply from their teen patient's bone marrow, before using chemotherapy to wipe out the remaining stem cells.

Then they used a modified virus to deliver an "anti-sickling" version of the beta globin gene into the stem cells they'd removed pre-chemo. The modified stem cells were infused back into the patient.

Over the next few months, the boy showed a growing number of new blood cells bearing the mark of the anti-sickling gene. The result was that roughly half of his hemoglobin was no longer abnormal.

In essence, Buchanan explained, the therapy "converted" the patient to sickle-cell trait that is, a person who carries only one copy of the abnormal hemoglobin gene. Those individuals don't develop sickle cell disease.

"This is encouraging," said Dr. David Williams, president of the Dana-Farber/Boston Children's Cancer and Blood Disorders Center.

But, he cautioned, "the caveat is, this is one patient, and 15 months is a short follow-up."

Williams and his colleagues are studying a different approach to sickle cell gene therapy. It aims to restart the body's production of healthy fetal hemoglobin to replace the abnormal "adult" hemoglobin seen in sickle cell.

If gene therapy is proven to work, there will no doubt be practical obstacles to its widespread use, according to Buchanan. It's a high-tech treatment, and many sickle cell patients are low-income and far from a major medical center, he said.

But, Buchanan said, the new findings have now "opened a door."

The study was partly funded by Bluebird Bio, the company developing the therapy.

The results were published in March in the New England Journal of Medicine.

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Gene therapy shows early promise against sickle cell - Chicago Tribune

Scientists have created an easy way to identify the state and fate of stem cells earlier than previously possible.

Understanding a stem cells fatethe type of cell it will eventually becomeand how far along it is in the process of development can help scientists better manipulate cells for stem cell therapy.

Having the ability to visualize a stem cells future will take some of the questions out of using stem cells to help regenerate tissue and treat diseases.

The beauty of the method is its simplicity and versatility, says Prabhas V. Moghe, a professor of biomedical engineering and chemical and biochemical engineering at Rutgers and senior author of a study published recently in the journal Scientific Reports. It will usher in the next wave of studies and findings.

Existing methods look at the overall population of cells but arent specific enough to identify individual cells fates. But when implanting stem cells (during a bone marrow transplant following cancer treatment, for example), knowing that each cell will become the desired cell type is essential.

Also, many protein markers used to distinguish cell types dont show up until after the cell has transitioned, which can be too late for some applications.

To identify earlier signals of a stem cells fate, scientists used super-resolution microscopy to analyze epigenetic modifications. Epigenetic modifications change how DNA is wrapped up within the nucleus, allowing different genes to be expressed.

Some modifications signal that a stem cell is transitioning into a particular type of cell, such as a blood, bone or fat cell. Using the new method, the team of scientists was able to determine a cells fate days before other techniques.

Having the ability to visualize a stem cells future will take some of the questions out of using stem cells to help regenerate tissue and treat diseases, says Rosemarie Hunziker, program director for tissue engineering and regenerative medicine at the National Institute of Biomedical Imaging and Bioengineering. Its a relatively simple way to get a jump on determining the right cells to use.

The approach, called EDICTS (Epi-mark Descriptor Imaging of Cell Transitional States), involves labeling epigenetic modifications and then imaging the cells with super resolution to see the precise location of the marks.

Were able to demarcate and catch changes in these cells that are actually not distinguished by established techniques such as mass spectrometry, Moghe says.

He described the method as fingerprinting the guts of the cell, and the results are quantifiable descriptors of each cells organization (for example, how particular modifications are distributed throughout the nuclei).

The team demonstrated the methods capabilities by measuring two types of epigenetic modifications in the nuclei of human stem cells cultured in a dish. They added chemicals that coaxed some of the cells to become fat cells and others to become bone, while another set served as control.

Within three days, the localization of the modifications varied in cells destined for different fates, two to four days before traditional methods could identify such differences between the cells. The technique had the specificity to look at regional changes within individual cells, while existing techniques can only measure total levels of modifications among the entire population of cells.

The levels are not significantly different, but how theyre organized is different and that seems to correlate with the fact that these cells are actually exhibiting different fates, Moghe says. It allows us to take out a single cell from a population of dissimilar cells, which can help researchers select particular cells for different stem cell applications.

The method is as easy as labeling, staining, and imaging cellstechniques already familiar to many researchers, he says. As the microscopes capable of super resolution imaging become more widely available, scientists can use it to sort and screen different types of cells, understand how a particular drug may disrupt epigenetic signaling, or ensure that stem cells to be implanted wont transform into the wrong cell type.

Collaborators are from Stanford University School of Medicine, Case Western Reserve University, Seoul National University, Princeton University, the University of Akron, the University of Pennsylvania, and MIT.

Source: Teal Burrell for the National Institute of Biomedical Imaging and Bioengineering via Rutgers University

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This simple method can predict a stem cell's fate - Futurity: Research News

THE family of a man urgently in need of a bonemarrow transplant has appealed to the Asian community to donate their stem cells in the hope of finding a suitable match to save his life.

Father of two, Yevi Ilangakoon, was diagnosed with myelofibrosis in 2009. It is a rare condition where scar tissue builds up inside the bone marrow, affecting its ability to create healthy blood cells, which affects one person in every 100,000.

The 63-year-old, who is originally from Sri Lanka and now lives in Whitstable, has seen his health deteriorate rapidly and his illness could now progress into leukemia if he is not treated.

His only option is to have a bone-marrow transplant using stem cells. However, specialists have been unable to find a 100 per cent match despite searching worldwide registers.

From the entire register, only four per cent are from a south Asian background.

Yevis son Yovaan told Eastern Eye: Its a lifethreatening disease and has been managed with medication for the past eight years, but the condition has got more and more aggressive, especially over the last few months. If he doesnt have a stem-cell transplant, it will be a few months to a year that he will have to live.

So it is quite crucial that we get as close to 100 per cent match as we can. He gets very, very tired because his hemoglobin levels are low. If he has an injury, it takes ages to heal. We are praying and being positive and trying to raise awareness.

Yovaan highlighted the issue on social media, which attracted the attention of Sri Lankan cricketer Mahela Jayawardena, but the family are still urging members of the public to get on the bone marrow register to find a match for Yevi.

The 29-year-old added: It could be your family member your mum or your dad, you dont know what position you are going to be in in a few years time.

If you are on the register, you have the chance of saving someones life. Its a really easy process.

Signing up online takes two minutes and participants simply need to swab the inside of their cheek with a cotton bud they are sent, and send it back in a pre-paid envelope.

Sarah Rogers of the Anthony Nolan charity said: We urgently need more people from Indian and South Asian backgrounds to register as stem cell donors to make sure that everyone, regardless of background, can receive a second chance at life.

At the moment we find a perfect match for about 60 per cent of northern European patients who need a transplant, but that drops to around 20 per cent for any patient of ethnic minority.

If you are above 30, go to: http://www.dkms.org.uk/en/ register-now. Under 30, register at http://www.anthonynolan.org/apply-join-bone-marrow-register.

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Family appeals for bone marrow donor to save father - Easterneye (press release) (subscription)

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Suicide Switch for Transplanted Stem Cells - The Scientist