Posted: April 13, 2015 at 6:40 pm
Human Stem Cells: A Potential Treatment for Huntington #39;s disease
Dr. Vicki Wheelock presents during Brain Awareness Week at University of California Davis Center for Neuroscience.
By: Center for Neuroscience, UC Davis
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Human Stem Cells: A Potential Treatment for Huntington's disease - Video
Posted: April 13, 2015 at 1:51 pm
Human Stem Cells: A Potential Treatment for Huntington #39;s disease
Dr. Vicki Wheelock presents during Brain Awareness Week at University of California Davis Center for Neuroscience.
By: Center for Neuroscience, UC Davis
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Human Stem Cells: A Potential Treatment for Huntington's disease - Video
Posted: April 13, 2015 at 1:51 pm
For millions of people around the world, who suffer from various diseases, research in stem cells offers a ray of hope. Scientists of the city-based Indian Institute of Science have used stem cells of a mouse to culture cardiac cells.
Explaining the research, Polani B. Seshagiri said their research over the past seven years has helped develop cardiac cells that function and beat in rhythms identical to the original cell.
Speaking on Stem Cell Awareness Day recently, Prof. Seshagiri said stem cells had several advantages and could cure human disorders and diseases, which could not be cured by conventional approaches. However, he warned that there was a need to be aware of the limitations of stem cells.
Sudarshan Ballal, Medical Director, Manipal Health Enterprise, said stem cells had enormous potential as they never die and could be converted into any cell. Stem cells can be converted into organs and maybe years later, organs can be cultivated in labs through stem cell, he said. Elaborating further, he said a stem cell could be compared to a bicycle, which could turn into car, motorbike and spaceship based on the environment and conditions.
Nazeer Ahmed, Deputy Drug Controller of Karnataka, said they were in the process of chalking out regulations for stem cells as there were currently no rules to regulate stem cell research and therapy.
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Scientists develop cardiac cells using stem cells
Posted: April 13, 2015 at 1:51 pm
SAN DIEGO -
Two years ago, Brenda Guerra's life changed forever.
"They told me that I went into a ditch and was ejected out of the vehicle," Guerra said.
The accident left the 26-year-old paralyzed from the waist down and confined to a wheelchair.
"I don't feel any of my lower body at all," she said.
Guerra has traveled from Kansas to UC San Diego to be the first patient to participate in a groundbreaking safety trial, testing stem cells for paralysis.
"We are directly injecting the stem cells into the spine," said Dr. Joseph D. Ciacci, professor of neurosurgery at UC San Diego.
The stem cells come from fetal spinal cords. The idea is when they're transplanted they will develop into new neurons and bridge the gap created by the injury by replacing severed or lost nerve connections. They did that in animals, and doctors are hoping for similar results in humans. The ultimate goal is to help people like Guerra walk again.
"The ability to walk is obviously a big deal not only in quality of life issues, but it also affects your survival long-term," Ciacci said.
Guerra received her injection and will be followed for five long years. She knows it's only a safety trial, but she's hoping for the best.
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Health Beat: Stem cells for paralysis: 1st of its kind study
Posted: April 13, 2015 at 1:51 pm
Targeted cancer therapies work by blocking a single oncogenic pathway to halt tumor growth. But because cancerous tumors have the unique ability to activate alternative pathways, they are often able to evade these therapies -- and regrow. Moreover, tumors contain a small portion of cancer stem cells that are believed to be responsible for tumor initiation, metastasis and drug resistance. Thus, eradicating cancer stem cells may be critical for achieving long-lasting remission, but there are no drugs available that specifically attack cancer stem cells.
Now a research team led by investigators in the Cancer Research Institute at Beth Israel Deaconess Medical Center (BIDMC), has identified an inhibitor of the Pin1 enzyme that can address both of these challenges in acute promyelocytic leukemia (APL) and triple negative breast cancer.
Their surprising discovery demonstrates that the vitamin A derivative ATRA (all-trans retinoic acid), a treatment for APL that is considered to be the first example of modern targeted cancer therapy, can block multiple cancer-driving pathways and, at the same time, eliminate cancer stem cells by degrading the Pin1 enzyme. Reported online in Nature Medicine, these novel findings suggest a promising new way to fight cancer -- particularly cancers that are aggressive or drug resistant.
"Pin1 changes protein shape through proline-directed phosphorylation, which is a major control mechanism for disease," explains co-senior author Kun Ping Lu, MD, PhD, Director of Translational Therapeutics in the Cancer Research Institute at BIDMC and Professor of Medicine at Harvard Medical School who co-discovered the enzyme in 1996. "Pin1 is a common key regulator in many types of cancer, and as a result, can control over 50 oncogenes and tumor suppressors, many of which are known to also control cancer stem cells."
Until now, agents that inhibit Pin1 have been developed mainly through rational drug design. Although these inhibitors have proven to be active against Pin1 in the test tube, when they are tested in vitro in a cell model or in vivo in a living animal they are unable to efficiently enter cells to successfully inhibit Pin1 function.
In this new work, co-senior author Xiao Zhen Zhou, MD, an investigator in BIDMC's Division of Translational Therapeutics and Assistant Professor at Harvard Medical School, decided to take a different approach to identify Pin1 inhibitors: She developed a mechanism-based high throughput screen to identify compounds that were targeting active Pin1.
"We had previously identified Pin1 substrate-mimicking peptide inhibitors," explains Zhou. "We therefore used these as a probe in a competition binding assay and screened approximately 8,200 chemical compounds, including both approved drugs and other known bioactive compounds." To increase screening success, Zhou chose a probe that specifically binds to the Pin1 enzyme active site very tightly, an approach that is not commonly used for this kind of screen.
"Initially, it appeared that the screening results had no positive hits, so we had to manually sift through them looking for the one that would bind to Pin1. We eventually spotted cis retinoic acid, which has the same chemical formula as all-trans retinoic acid [ATRA], but with a different chemical structure." It turned out, Zhou explains, that Pin1 prefers binding to ATRA and cis retinoic acid needs to convert ATRA in order to bind Pin1.
ATRA was first discovered for the treatment of acute promyelocytic leukemia (APL) in 1987. "Before tamoxifen or other targeted drugs, there was ATRA," says Lu. It was originally thought that ATRA was successfully treating APL by inducing cell differentiation, causing cancer cells to change into normal cells by activating the cellular retinoic acid receptors. But as these new findings reveal, although this differentiation activity is obvious, it is not the mechanism that is actually behind ATRA's successful outcomes in treating APL.
"While it has been previously shown that ATRA's ability to degrade the leukemia-causing fusion oncogene PML-RAR causes ATRA to stop the leukemia stem cells that drive APL, the underlying mechanism has remained elusive," says Lu. "Our new high throughput drug screening has revealed the ATRA drug target, unexpectedly showing that ATRA directly binds, inhibits and ultimately degrades active Pin1 selectively in cancer cells. The Pin1-ATRA complex structure suggests that ATRA is trapped in the Pin1 active site by mimicking an unreleasable enzyme substrate. Importantly, ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RAR and treats APL in cell and animal models as well as in human patients.
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Researchers identify drug target for ATRA, the first precision cancer therapy
Posted: April 13, 2015 at 1:44 pm
BioLife Solutions, Inc. (NASDAQ: BLFS), a leading developer, manufacturer and marketer of proprietary clinical grade hypothermic storage and cryopreservation freeze media and precision thermal shipping products for cells and tissues (BioLife or the Company), today announced that Cardio3 BioSciences, a leader in engineered cell therapy with clinical programs initially targeting indications in cardiovascular disease and oncology, has embedded the Companys clinical grade CryoStor cryopreservation freeze media in its ongoing Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) phase III clinical trial in Europe and Israel and the pending CHART-2 phase III clinical trial to be conducted in the United States.
CHART-1 (Congestive Heart Failure Cardiopoietic Regenerative Therapy) is a patient prospective, controlled multi-centre, randomized, double-blinded Phase III clinical trial comparing treatment with C-Cure to a sham treatment. The trial has recruited 240 patients with chronic advanced symptomatic heart failure. The primary endpoint of the trial is a composite endpoint including mortality, morbidity, quality of life, Six Minute Walk Test and left ventricular structure and function at nine months post-procedure.
Dr. Christian Homsy, CEO of Cardio3 BioSciences, commented on the selection of CryoStor by stating, We evaluated several possible freeze media formulations for our clinical cell therapy product development and manufacturing. CryoStor and BioLife best met our preservation efficacy, product and supplier quality, and customer support requirements.
As of January 2015, BioLife management estimates that the Companys CryoStor freeze media and HypoThermosol cell and tissue storage/shipping media have been incorporated into at least 175 customer clinical trials of novel cellular immunotherapies and other cell-based approaches for treating and possibly curing the leading causes of death and disorders throughout the world. Within the cellular immunotherapy segment of the regenerative medicine market, BioLife's products are embedded in the manufacturing, storage, and delivery processes of at least 75 clinical trials of chimeric antigen receptor T cells (CAR-T), T cell receptor (TCR), dendritic cell (DC), tumor infiltrating lymphocytes (TIL), and other T cell-based cellular therapeutics targeting solid tumors, hematologic malignancies, and other diseases and disorders. A large majority of the currently active private and publicly traded cellular immunotherapy companies are BioLife customers.
Mike Rice, BioLife Solutions CEO, remarked; We are honored to be able to supply our clinical grade CryoStor cell freeze media for Cardio3 Biosciences phase III clinical trials. Congestive heart failure is a leading cause of death and C-Cure is a novel and potentially life-saving, cell-based therapy that offers hope to millions of patients throughout the world. We are very well positioned to participate in the growth of the regenerative medicine market, with our products being used in at least 75 phase II and over 20 phase III clinical trials of new cell and tissue based products and therapies.
About Cardio3 Biosciences Cardio3 BioSciences is a leader in engineered cell therapy with clinical programs initially targeting indications in cardiovascular disease and oncology. Founded in 2007 and based in the Walloon region of Belgium, Cardio3 BioSciences leverages research collaborations in the USA with the Mayo Clinic (MN, USA) and Dartmouth College (NH, USA). The Companys lead product candidate in cardiology is C-Cure, an autologous stem cell therapy for the treatment of ischemic heart failure. The Companys lead product candidate in oncology is CAR- NKG2D, an autologous CAR T-cell product candidate using NKG2D, a natural killer cell receptor designed to target ligands present on multiple tumor types, including ovarian, bladder, breast, lung and liver cancers, as well as leukemia, lymphoma and myeloma. Cardio3 BioSciences is also developing medical devices for enhancing the delivery of diagnostic and therapeutic agents into the heart (CCath) and potentially for the treatment of mitral valve defects. Cardio3 BioSciences shares are listed on Euronext Brussels and Euronext Paris under the ticker symbol CARD. To learn more about Cardio3 BioSciences, please visit c3bs.com
About C-Cure Cardio3 BioSciences C-Cure therapy involves taking stem cells from a patients own bone marrow and through a proprietary process called Cardiopoiesis, re-programming those cells to become heart cells. The cells, known as cardiopoietic cells, are then injected back into the patients heart through a minimally invasive procedure, with the aim of repairing damaged tissue and improving heart function and patient clinical outcomes. C-Cure is the outcome of multiple years of research conducted at Mayo Clinic (Rochester, Minnesota, USA), Cardio3 BioSciences (Mont-Saint-Guibert, Belgium) and Cardiovascular Centre in Aalst (Aalst, Belgium). C-Cure is currently in Phase III clinical trials (CHART-1, approved by the EMA and CHART-2, for which enrollment will begin once final approval is received from FDA). The results of the Phase II trial, completed in January 2012, were published in the Journal of the American College of Cardiology (JACC) in April 2013. The publication reported a significant improvement in treated patients.
About BioLife Solutions BioLife Solutions develops, manufactures and markets hypothermic storage and cryopreservation solutions and precision thermal shipping products for cells, tissues, and organs. BioLife also performs contract aseptic media formulation, fill, and finish services. The Companys proprietary HypoThermosol and CryoStor biopreservation media products are highly valued in the biobanking, drug discovery, and regenerative medicine markets. BioLifes proprietary products are serum-free and protein-free, fully defined, and are formulated to reduce preservation-induced cell damage and death. This enabling technology provides commercial companies and clinical researchers significant improvement in shelf life and post-preservation viability and function of cells, tissues, and organs. For more information please visit http://www.biolifesolutions.com, and follow BioLife on Twitter.
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CryoStor Cell Preservation Selected For Phase III Clinical Trials of C-Cure Cell Therapy for Congestive Heart Failure
Posted: April 13, 2015 at 1:42 pm
Findings from animal study have implications for disorders such as chronic obstructive pulmonary disease
IMAGE:Adult lung cells regenerating: Type 1 cells are green. Type 2 cells are red. New Type 2 derived from Type 1 cells are yellow. Nuclei are blue view more
Credit: Jon Epstein, MD & Rajan Jain, MD, Perelman School of Medicine at the University of Pennsylvania, and Christina Barkauskas & Brigid Hogan, Duke University
PHILADELPHIA - A new collaborative study describes a way that lung tissue can regenerate after injury. The team found that lung tissue has more dexterity in repairing tissue than once thought. Researchers from the Perelman School of Medicine at the University of Pennsylvania and Duke University, including co-senior authors Jon Epstein, MD, chair of the department of Cell and Developmental Biology, and Brigid L.M Hogan, Duke Medicine, along with co-first authors Rajan Jain, MD, a cardiologist and instructor in the Department of Medicine and Christina E. Barkauskas, also from Duke, report their findings in Nature Communications
"It's as if the lung cells can regenerate from one another as needed to repair missing tissue, suggesting that there is much more flexibility in the system than we have previously appreciated," says Epstein. "These aren't classic stem cells that we see regenerating the lung. They are mature lung cells that awaken in response to injury. We want to learn how the lung regenerates so that we can stimulate the process in situations where it is insufficient, such as in patients with COPD [chronic obstructive pulmonary disease]."
The two types of airway cells in the alveoli, the gas-exchanging part of the lung, have very different functions, but can morph into each other under the right circumstances, the investigators found. Long, thin Type 1 cells are where gases (oxygen and carbon dioxide) are exchanged - the actual breath. Type 2 cells secrete surfactant, a soapy substance that helps keep airways open. In fact, premature babies need to be treated with surfactant to help them breathe.
The team showed in mouse models that these two types of cells originate from a common precursor stem cell in the embryo. Next, the team used other mouse models in which part of the lung was removed and single cell culture to study the plasticity of cell types during lung regrowth. The team showed that Type 1 cells can give rise to Type 2 cells, and vice-versa.
The Duke team had previously established that Type 2 cells produce surfactant and function as progenitors in adult mice, demonstrating differentiation into gas-exchanging Type 1 cells. The ability of Type I cells to give rise to alternate lineages had not been previously reported.
"We decided to test that hypothesis about Type 1 cells," says Jain. "We found that Type 1 cells give rise to the Type 2 cells over about three weeks in various models of regeneration. We saw new cells growing back into these new areas of the lung. It's as if the lung knows it has to grow back and can call into action some Type 1 cells to help in that process."
This is one of the first studies to show that a specialized cell type that was thought to be at the end of its ability to differentiate can revert to an earlier state under the right conditions. In this case, it was not by using a special formula of transcription factors, but by inducing damage to tell the body to repair itself and that it needs new cells of a certain type to do that.
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One type of airway cell can regenerate another lung cell type
Posted: April 13, 2015 at 1:41 pm
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Newswise PHILADELPHIA A new collaborative study describes a way that lung tissue can regenerate after injury. The team found that lung tissue has more dexterity in repairing tissue than once thought. Researchers from the Perelman School of Medicine at the University of Pennsylvania and Duke University, including co-senior authors Jon Epstein, MD, chair of the department of Cell and Developmental Biology, and Brigid L.M Hogan, Duke Medicine, along with co-first authors Rajan Jain, MD, a cardiologist and instructor in the Department of Medicine and Christina E. Barkauskas, also from Duke, report their findings in Nature Communications.
Its as if the lung cells can regenerate from one another as needed to repair missing tissue, suggesting that there is much more flexibility in the system than we have previously appreciated, says Epstein. These arent classic stem cells that we see regenerating the lung. They are mature lung cells that awaken in response to injury. We want to learn how the lung regenerates so that we can stimulate the process in situations where it is insufficient, such as in patients with COPD [chronic obstructive pulmonary disease].
The two types of airway cells in the alveoli, the gas-exchanging part of the lung, have very different functions, but can morph into each other under the right circumstances, the investigators found. Long, thin Type 1 cells are where gases (oxygen and carbon dioxide) are exchanged the actual breath. Type 2 cells secrete surfactant, a soapy substance that helps keep airways open. In fact, premature babies need to be treated with surfactant to help them breathe.
The team showed in mouse models that these two types of cells originate from a common precursor stem cell in the embryo. Next, the team used other mouse models in which part of the lung was removed and single cell culture to study the plasticity of cell types during lung regrowth. The team showed that Type 1 cells can give rise to Type 2 cells, and vice-versa.
The Duke team had previously established that Type 2 cells produce surfactant and function as progenitors in adult mice, demonstrating differentiation into gas-exchanging Type 1 cells. The ability of Type I cells to give rise to alternate lineages had not been previously reported.
We decided to test that hypothesis about Type 1 cells, says Jain. We found that Type 1 cells give rise to the Type 2 cells over about three weeks in various models of regeneration. We saw new cells growing back into these new areas of the lung. Its as if the lung knows it has to grow back and can call into action some Type 1 cells to help in that process.
This is one of the first studies to show that a specialized cell type that was thought to be at the end of its ability to differentiate can revert to an earlier state under the right conditions. In this case, it was not by using a special formula of transcription factors, but by inducing damage to tell the body to repair itself and that it needs new cells of a certain type to do that.
The team is also applying the approaches outlined in this paper to cells in the intestine and skin to study basic ideas of stem cell maintenance and differentiation to relate back to similar mechanisms in the heart. They also hope to apply this knowledge to such other lung conditions as acute respiratory distress syndrome and idiopathic pulmonary fibrosis, where the alveoli cannot get enough oxygen into the blood.
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Limber Lungs: One Type of Airway Cell Can Regenerate Another Lung Cell Type
Posted: April 12, 2015 at 7:03 pm
Asterias Biotherapeutics
Pedro Lichtinger, President CEO (NYSEMKT: AST) Headquarters: Menlo Park, CA Asterias develops products based on its core technology platforms of pluripotent stem cells and allogeneic dendritic.
By: Alliance for Regenerative Medicine
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Asterias Biotherapeutics - Video
Posted: April 12, 2015 at 6:53 pm
Parkinson's is an incurable progressive condition of the brain. It affects movement, speech and balance and causes incessant shivering of the face and limbs. Genetic and environmental factors are believed to contribute to the degeneration of brain cells that maintain bodily movement. There is no particular test to detect the disease, with only physical symptoms enabling doctors to make a diagnosis.
After 15 years of suffering and two failed stem cell transplantation surgeries, a 68-year-old businessman finally decided to undergo surgery on the eve of World Parkinson's Day at Jaslok Hospital. According to the doctors, the businessman, who is from Gujarat, had uncontrolled Parkinson's disease (PD) and was lured by the temptation of finding a 'cure' for the disease.
"He was lured by the temptation of finding a 'cure' for Parkinson's disease he underwent intracranial stem cell transplantation (a neurosurgical procedure) in Bangalore. As he did not obtain any benefit, he was given a 'top up' by the intravenous stem cell route. Obviously, none of these worked and his disease progressed," said Dr Paresh Doshi, Director, Neurosurgery Department at Jaslok Hospital.
As the disease progressed, Jain decided to go for deep brain stimulation (DBS) surgery, a standard surgical treatment for PD. "He had unbearable stiffness and discomfort and was taking large doses of medications. With the disease being in an advanced stage, DBS surgery was the only option," said Dr Doshi.
Since Jain had already undergone two operations, the team of neurosurgeons had a tough time executing the surgery. "Jain's case was tricky as the area we were interested in had already been operated on. Advanced technology and expertise helped us find our way into the brain and successfully accomplish the surgery," said Dr Doshi.
While Jain is now recuperating at the hospital, Dr Doshi said he is a classic example of poor awareness on PD. "The important message to convey is that stem cell treatment is a still at the laboratory stage. It can be tested on humans only after careful animal experimentation. So far, the efficacy of the stem cell therapy hasn't been proven and people shouldn't get misled," he said.
Neurologists say PD affects roughly one lakh people in India most of them over the age of 50, although it can sometimes affect younger adults. Awareness about the disease is a must in India, as the number of PD cases affecting those over the age of 60 are increasing sharply. "Parkinson's affects one in hundred individuals. While 55 crore Indians over 60 were afflicted in 2013, the number is estimated to triple to 160 crores by 2050. By then, over 22% of the Indian population will comprise of the elderly. It is therefore important to have more awareness on management of the disease," said Dr Doshi.
Dr Maria Barretto, CEO of Parkinson's Disease and Movement Disorder Society (PDMDS), which has twenty support groups in India including in Mumbai, Nasik and Baroda, agreed on poor general awareness about PD. "At PDMDS, we conduct various programs to spread awareness on the disease among both caregivers and the patients," she said.
Dr Charulata Sankhla, neurophysician at PD Hinduja Hospital who is also part of PDMDS, said that PD cases may be underreported due to lack of awareness. "Patients come to us very late because they don't recognise the symptoms. PD has to be diagnosed early, and it is very important to keep the patient active to ensure s/he has better mobility and a longer life."
Talking about surgery intervention, Dr Sankhla added that doctors would earlier wait for 5-6 years before taking a patient for surgery. However, surgery is being opted for in 3-4 years post the onset of PD. "Patients need to approach neurophysicians at the earliest so that it can be determined which stage of the disease the patient falls in. Treatment and surgery are recommended accordingly."
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Awareness about Parkinson's disease on shaky ground
