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New approach to assessing effectiveness of anti-cancer drugs

By Stem Cell Doctors

Manchester scientists have a developed a new method to monitor the effect of anti-cancer drugs on very rare leukemia stem cells. The approach potentially allows doctors to screen patients and personalise their treatment.

The recent development of novel agents has improved outcomes for patients with chronic myeloid leukemia (CML). These so-called tyrosine kinase inhibitors (TKIs) target abnormal proteins caused by commonly found genetic mutations in CML patients. However, the existence of treatment-resistant cancer stem cells -- cells that are able to repeatedly renew the leukemia cell population -- is one way that many patients experience disease recurrence when treatment stops.

Any new drug must therefore be tested on such stem cells, but unfortunately they are only found in very low numbers and are identified by certain cell surface markers. Now researchers at The University of Manchester -- part of the Manchester Cancer Research Centre -- have tested a way to monitor the effect of drugs on small samples of cells.

Professor Tony Whetton, head of the Stem Cell and Leukaemia Proteomics Laboratory who led the study, said: "Current techniques require greater numbers of cells in order to detect changes caused by TKIs. Our study investigated the potential of a new technology platform that can identify changes in very small cell numbers."

The research team looked at an antibody-based approach to detect structural changes in certain proteins, in order to track the effectiveness of the TKI drugs. The instrument used fixes proteins in place and holds them, there allowing for a better signal to be generated from less material. With this approach they found that they could record changes in samples of only a few thousand critically important but rare stem cells.

"This new approach will enable us to test drugs on cells taken from patients, either at presentation or in a clinical trial setting. It has great potential to allow us to implement precision medicine, where patients receive the most appropriate treatment to target their individual tumour," added Professor Whetton.

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Neurons Controlling Appetite Made From Skin Cells

By Stem Cell Medical Center

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Newswise NEW YORK, NY (February 27, 2015) Researchers have for the first time successfully converted adult human skin cells into neurons of the type that regulate appetite, providing a patient-specific model for studying the neurophysiology of weight control and testing new therapies for obesity. The study, led by researchers at Columbia University Medical Center (CUMC) and at the New York Stem Cell Foundation (NYSCF), was published last month in the online issue of the Journal of Clinical Investigation.

In a separate study, which appeared in the February 10 issue of the journal Development, Kevin Eggan, PhD, Florian Merkle, and Alexander Schier of Harvard University have also succeeded in creating hypothalamic neurons from iPS cells. These neurons help to regulate behavioral and basic physiological functions in the human body, including, in addition to appetite, hypertension, sleep, mood, and some social disorders. The investigators at Columbia and Harvard shared ideas during the course of the research, and these studies are co-validating.

Mice are a good model for studying obesity in humans, but it would better to have human cells for testing. Unfortunately, the cells that regulate appetite are located in an inaccessible part of the brain, the hypothalamus. So, until now, weve had to make do with a mouse model or with human cells harvested at autopsy. This has greatly limited our ability to study fundamental aspects of human obesity, said senior author Rudolph L. Leibel, MD, the Christopher J. Murphy Memorial Professor of Diabetes Research, professor of pediatrics and medicine, and co-director of the Naomi Berrie Diabetes Center at CUMC.

To make the neurons, human skin cells were first genetically reprogrammed to become induced pluripotent stem (iPS) cells. Like natural stem cells, iPS cells are capable of developing into any kind of adult cell when given a specific set of molecular signals in a specific order. The iPS cell technology has been used to create a variety of adult human cell types, including insulin-producing beta cells and forebrain and motor neurons. But until now, no one has been able to figure out how to convert human iPS cells into hypothalamic neurons, said co-author Dieter Egli, PhD, assistant professor of pediatrics (in developmental cell biology), a member of the Naomi Berrie Diabetes Center, and a senior research fellow at NYSCF.

This is a wonderful example of several institutions coming together to collaborate and advance research in pursuit of new therapeutic interventions. The ability to make this type of neuron brings us one step closer to the development of new treatments for obesity, said Susan L. Solomon, CEO of NYSCF.

The CUMC/NYSCF team determined which signals are needed to transform iPS cells into arcuate hypothalamic neurons, a neuron subtype that regulates appetite. The transformation process took about 30 days. The neurons were found to display key functional properties of mouse arcuate hypothalamic neurons, including the ability to accurately process and secrete specific neuropeptides and to respond to metabolic signals such as insulin and leptin.

We dont think that these neurons are identical to natural hypothalamic neurons, but they are close and will still be useful for studying the neurophysiology of weight control, as well as molecular abnormalities that lead to obesity, said Dr. Leibel. In addition, the cells will allow us to evaluate potential obesity drugs in a way never before possible.

This shows, said Dr. Eggan, how improved understanding of stem cell biology is making an impact on our ability to study, understand, and eventually treat disorders of the nervous system. Because there are so few hypothalamic neurons of a given type, they have been notoriously difficult to study. The successful work by both groups shows that this problem has been cracked.

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Neurons Controlling Appetite Made From Skin Cells

Small molecule helps get stem cells to sites of disease and damage

By Stem Cell Clinic

An industry-academic research collaboration yields a new strategy for delivering stem cells to the right location

IMAGE:Researchers identified a small molecule that can be used to program mesenchymal stem cells (blue and green) to home in on sites of damage. view more

Credit: Oren Levy, Brigham and Women's Hospital

Bioengineers from Brigham and Women's Hospital (BWH) with collaborators at the pharmaceutical company Sanofi have identified small molecules that can be used to program stem cells to home in on sites of damage, disease and inflammation. The techniques used to find and test these small molecules may represent important tools in advancing cell-based therapy, offering a new strategy for delivering cells to the right locations in the body. The results of their work appear online this week in Cell Reports.

Through a collaborative research project, the research team tested more than 9,000 compounds, and used a multi-step approach - including a sophisticated microfluidics set up and novel imaging technique - to narrow in on and test the most promising compounds.

"There are all kinds of techniques and tools that can be used to manipulate cells outside of the body and get them to do almost anything we want, but once we transplant cells we lose complete control over them," said co-senior author Jeff Karp, PhD, an associate professor at BWH, Harvard Medical School, and principal faculty at the Harvard Stem Cell Institute. "Through this collaboration, we've been able to identify small molecules that can be used to treat cells outside of the body, programming them to target blood vessels in diseased or damaged tissue."

Small molecules offered the team several advantages including the ability to use a safe and relatively simple procedure to pre-treat the cells before injecting them intravenously.

"There's a great need to develop strategies that improve the clinical impact of cell-based therapies," said co-first author Oren Levy, PhD, an instructor in medicine at BWH. "If you can create an engineering strategy that is safe, cost effective and simple to apply, that's exactly what we need to achieve the promise of cell-based therapy."

Karp's team at the Brigham had previously found that it is possible to use bioengineering techniques to chemically attach molecules to the surface of a cell that act as a GPS, guiding the cell to the site of inflammation. These findings indicated that targeted delivery of cells was possible, but a scalable approach would be needed to impact patients.

"At BWH, we had laid the groundwork. Our collaborators at Sanofi have complementary expertise in screening for small molecules, deep understanding of the biology and unmet needs, and an exceptional ability to bring new therapeutics to the clinic," said Karp. "Defined goals and both teams working seamlessly together created perfect synergy. We learned so much from each other."

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Small molecule helps get stem cells to sites of disease and damage

Stem cell therapy a boon to Parkinson's patients

By Uncategorized

Bengaluru:Feb 27, 2015, DHNS

Two courses of stem cell therapy have helped Ashok Kumar, 59, who suffered from tremors and rigidity due to Parkinsons disease, recover completely, much to the joy of his family. The man was brought inside my cabin in a wheelchair. He was unable to even sit on the chair without support. Today, he walks independently. Stem cell therapy has made it possible for him, said Dr Naseem Sadiq, Director, Plexus Neuro and Stem Cell Research Centre, who began treating Kumar in October, last year.

Previously, medication and surgical procedure were the only treatment option for Parkinsons disease. Medication in the long-term often lacks effectiveness and may cause side effects, while surgery is not always feasible. Lately, stem cell therapy has turned out to be a boon for patients with Parkinsons, Dr Sadiq said.

Kumar is among the few who have benefited from stem cell therapy. However, though the State has been reporting an increase in the number of registered stem cell donors, it is far behind sufficient as the genetic match between donor and recipient could be anywhere between one in 10,000 and one in two million, according to experts.

Speaking to Deccan Herald, Raghu Rajgopal, co-founder, Datri, a registry for stem cell donation, said, The response we get from Karnataka when we conduct stem cell camps is great. We see a lot of people and registering with us.

As many as 6,000 people have registered from the State under the Datri registry. A total of 72,000 people have registered across the country. In Kerala, 11,000 have signed up, the highest so far, he said.

Among the common myths are that by donating stem cells one turns infertile and weak, have increased chances of cancer and also that there would be excess loss of blood, he said.

According to studies, over one lakh people are diagnosed with Leukemia (blood cancer) and other blood disorders every year in India. The Indian Council of Medical Research has predicted that by the end of 2015, Leukemia cases will reach an estimated 1,17,649 and 1,32,574 by 2020. Stem cell therapy is a widely used treatment mechanism for Leukemia.

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Progencell | Stem Cell Therapy | Tijuana Mexico

By Stem Cell Treatment

WELCOME TO PROGENCELL-STEM CELL THERAPIES

Congratulations on taking the first step to improving your health!

PROGENCELL offers stem cell protocols with effective results. Many years of research and experience have resulted in substantial improvements in the health and conditions of patients with various diseases, even where other treatments have failed.

With the highest quality protocols, Progencell uses stem cells directly from the patient (autologous adult stem cells) in order to improve their health. The patients medical condition creates the appropriate environment in the body, resulting in a personalized therapy created specially for him.

We offer patients with certain degenerative diseases an opportunity to improve their health through cellular therapy, correcting their medical conditions from the source by regenerating the tissues and organs that are causing the ailments. Since we use stem cells from the patient, this therapy has no risk of tissue rejection, and minimal secondary effects.

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Quality control for adult stem cell treatment

By Stem Cell Treatment

A team of European researchers has devised a strategy to ensure that adult epidermal stem cells are safe before they are used as treatments for patients. The approach involves a clonal strategy where stem cells are collected and cultivated, genetically modified and single cells isolated before being rigorously tested to make sure they meet the highest possible safety criteria. The strategy, which is published online in EMBO Molecular Medicine, is inspired by the approaches the biotechnology industry and regulatory affairs authorities have adopted for medicinal proteins produced from genetically engineered mammalian cells.

"Until now there has not been a systematic way to ensure that adult epidermal stem cells meet all the necessary requirements for safety before use as treatments for disease," says EMBO Member Yann Barrandon, Professor at Lausanne University Hospital, the Swiss Federal Institute of Technology in Lausanne and the lead author of the study. "We have devised a single cell strategy that is sufficiently scalable to assess the viability and safety of adult epidermal stem cells using an array of cell and molecular assays before the cells are used directly for the treatment of patients. We have used this strategy in a proof-of-concept study that involves treatment of a patient suffering from recessive dystrophic epidermolysis bullosa, a hereditary condition defined by the absence of type VII collagen which leads to severe blistering of the skin."

The researchers cultivated epidermal cells from the patient that can be used to regenerate skin. The scientists used their array of tests to determine which of the transduced cells met the necessary requirements for stemness -- the characteristics of a stem cell that distinguish it from a regular cells -- and safety. Clonal analysis revealed that the transduced stem cells varied in their ability to produce functional type VII collagen. When the most viable, modified stem cells were selected, transplantation onto immunodeficient mice regenerated skin that did not blister in the mouse model system for recessive dystrophic epidermolysis bullosa and produced functional type VII collagen. Safety was assessed by determining the sites of integration of the viral vector, looking for rearrangements and hit genes, as well as whole genome sequencing.

"Our work shows that at least for adult epidermal stem cells it is possible to use a clonal strategy to deliver a level of safety that cannot be obtained by other gene therapy approaches. A clonal strategy should make it possible to integrate some of the more recent technologies for targeted genome editing that offer more precise ways to change genes in ways that may further benefit the treatment of disease. Further work is in progress in this direction."

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Quality control for adult stem cell treatment

The Irvine Stem Cell Treatment Center Announces Adult Stem Cell Public Seminars in Riverside, Ontario, and Brea …

By Stem Cell Treatment

Riverside, ON and Brea CA (PRWEB) February 26, 2015

The Irvine Stem Cell Treatment Center announces a series of free public seminars on the use of adult stem cells for various degenerative and inflammatory conditions. They will be provided by Dr. Thomas A. Gionis, Surgeon-in-Chief.

The seminars will be held on Saturday, March 7, 2015, at 11:00 am, 1:00 pm and 3:00 pm at Courtyard Riverside Downtown / Marriott, 1510 University Avenue, Riverside, CA 92507; Tuesday, March 10, 2015, at 11:00 am, 1:00 pm and 3:00 pm at Ayres Suites Ontario at the Mills Mall, 4370 Mills Circle, Ontario, CA 91764; and Saturday, March 21, 2015, at 11:00 am, 1:00 pm and 3:00 pm at Embassy Suites Hotel, 900 E Birch Street, Brea, CA 92821. Please RSVP at (949) 679-3889.

The Irvine Stem Cell Treatment Center (Irvine and Westlake), along with sister affiliates, the Miami Stem Cell Treatment Center (Miami; Boca Raton; Orlando; The Villages, Florida) and the Manhattan Regenerative Medicine Medical Group (Manhattan, New York), abide by approved investigational protocols using adult adipose derived stem cells (ADSCs) which can be deployed to improve patients quality of life for a number of chronic, degenerative and inflammatory conditions and diseases. ADSCs are taken from the patients own adipose (fat) tissue (found within a cellular mixture called stromal vascular fraction (SVF)). ADSCs are exceptionally abundant in adipose tissue. The adipose tissue is obtained from the patient during a 15 minute mini-liposuction performed under local anesthesia in the doctors office. SVF is a protein-rich solution containing mononuclear cell lines (predominantly adult autologous mesenchymal stem cells), macrophage cells, endothelial cells, red blood cells, and important Growth Factors that facilitate the stem cell process and promote their activity.

ADSCs are the bodys natural healing cells - they are recruited by chemical signals emitted by damaged tissues to repair and regenerate the bodys injured cells. The Irvine Stem Cell Treatment Center only uses Adult Autologous Stem Cells from a persons own fat No embryonic stem cells are used; and No bone marrow stem cells are used. Current areas of study include: Emphysema, COPD, Asthma, Heart Failure, Heart Attack, Parkinsons Disease, Stroke, Traumatic Brain Injury, Lou Gehrigs Disease, Multiple Sclerosis, Lupus, Rheumatoid Arthritis, Crohns Disease, Muscular Dystrophy, Inflammatory Myopathies, and degenerative orthopedic joint conditions (Knee, Shoulder, Hip, Spine). For more information, or if someone thinks they may be a candidate for one of the adult stem cell protocols offered by the Irvine Stem Cell Treatment Center, they may contact Dr. Gionis directly at (949) 679-3889, or see a complete list of the Centers study areas at: http://www.IrvineStemCellsUSA.com.

About the Irvine Stem Cell Treatment Center: The Irvine Stem Cell Treatment Center, along with sister affiliates, the Miami Stem Cell Treatment Center and the Manhattan Regenerative Medicine Medical Group, is an affiliate of the California Stem Cell Treatment Center / Cell Surgical Network (CSN); we are located in Irvine and Westlake, California. We provide care for people suffering from diseases that may be alleviated by access to adult stem cell based regenerative treatment. We utilize a fat transfer surgical technology to isolate and implant the patients own stem cells from a small quantity of fat harvested by a mini-liposuction on the same day. The investigational protocols utilized by the Irvine Stem Cell Treatment Center have been reviewed and approved by an IRB (Institutional Review Board) which is registered with the U.S. Department of Health, Office of Human Research Protection (OHRP); and our studies are registered with Clinicaltrials.gov, a service of the U.S. National Institutes of Health (NIH). For more information, visit our websites: http://www.IrvineStemCellsUSA.com, http://www.MiamiStemCellsUSA.com, or http://www.NYStemCellsUSA.com.

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The Irvine Stem Cell Treatment Center Announces Adult Stem Cell Public Seminars in Riverside, Ontario, and Brea ...

Moffitt Cancer Center Researchers Identify Protein Pathway Involved in Brain Tumor Stem Cell Growth

By Stem Cell Treatment

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Newswise TAMPA, Fla. Glioblastomas are a highly aggressive type of brain tumor, with few effective treatment options. Moffitt Cancer Center researchers are one step closer to understanding glioblastoma development following the identification of a key protein signaling pathway involved in brain tumor stem cell growth and survival. Brain tumor stem cells are believed to play an important role in glioblastoma development and may be possible therapeutic targets.

The neurotrophin protein pathway controls nerve growth, survival and specialization. In an article published in the Feb. 6 issue of The Journal of Biological Chemistry, Moffitt researchers reported that the neurotrophin pathway is also involved in the survival and growth of brain tumor stem cells. The stem cells have high levels of neurotrophin receptors called TrkB and TrkC. Cellular signals from normal brain cells can activate TrkB and TrkC on the stem cells and stimulate cell growth. And when scientists inhibited TrkB and TrkC, they found decreased stem cell survival. This suggests that TrkB and TrkC may be possible drug targets for stem cells in gliomas and glioblastomas.

This work might be a first step in developing new treatment approaches targeting brain tumor stem cells. It may also partly explain why brain tumors can grow so quickly since proteins from the surrounding normal brain might be used by the tumor to grow even faster, said Peter A. Forsyth, M.D., chair of the Department of Neuro-Oncology at Moffitt.

Researchers also reported a potential reason why several clinical trials targeting a protein called EGFR in glioblastoma patients have failed to live up to expectations. EGFR is frequently activated in glioblastoma, but results from trials using EGFR inhibitors showed little or no patient improvement. Moffitt scientists discovered that TrkB and TrkC maintain brain stem cell survival and growth even when EGFR inhibitors are used. These observations suggest that one reason why EGFR inhibitors may be ineffective in glioblastoma is that TrkB and TrkC are active, thereby bypassing EGFR inhibition and allowing stem cells to continue to grow.

This is the first time that scientists have shown that TrkB and TrkC are involved in brain tumor stem cell growth. Currently, no drugs that target TrkB and TrkC have been used as brain cancer treatments. Researchers hope that these results might encourage the development of drugs that target both the stem cell compartment and the more differentiated parts of the brain tumor and result in more effective therapies.

The study was supported by funds The V Foundation for Cancer Research and the Moffitt Cancer Center Foundation.

About Moffitt Cancer Center: Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitts excellence in research, its contributions to clinical trials, prevention and cancer control. Moffitt is the top-ranked cancer hospital in the Southeast and has been listed in U.S. News & World Reports Best Hospitals for cancer care since 1999. With more than 4,500 employees, Moffitt has an economic impact in Florida of nearly $1.6 billion. For more information, visit MOFFITT.org, and follow the Moffitt momentum on Facebook, Twitter and YouTube.

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Moffitt Cancer Center Researchers Identify Protein Pathway Involved in Brain Tumor Stem Cell Growth

Culture clash: How stem cells are grown affects their genetic stability

By Stem Cell Medicine

Methods to multiply pluripotent cells for potential therapies raise worries about cancer

The therapeutic promise of human stem cells is indisputably huge, but the process of translating their potential into effective, real-world treatments involves deciphering and resolving a host of daunting complexities.

Writing in the February 25 online issue of the journal PLOS ONE, researchers at University of California, San Diego School of Medicine, with collaborators from The Scripps Research Institute (TSRI), have definitively shown for the first time that the culture conditions in which stem cells are grown and mass-produced can affect their genetic stability.

"Since genetic and epigenetic instability are associated with cancers, we worry that similar alterations in stem cells may affect their safety in therapeutic transplants. Certain mutations might make transplanted stem cells more likely to form tumors, introducing the risk of cancer where it didn't exist before," said co-corresponding author Louise Laurent, MD, PhD, assistant professor and director of perinatal research in the Department of Reproductive Medicine at UC San Diego School of Medicine.

"This study shows the importance of quality control," added Jeanne F. Loring, PhD, professor and director of the Center for Regenerative Medicine at TSRI, and adjunct professor in the UC San Diego Department of Reproductive Medicine and the study's other co-corresponding author. "It's almost certain these cells are safe, but we want to make sure they are free from any abnormalities."

To exploit the transformative powers of human pluripotent stem cells, which include embryonic stem cells and induced pluripotent stem cells, requires producing them in large numbers for transplantation into patients.

"During this culturing process, mutations can occur, and mutations that increase cell survival or proliferation may be favored, such that the cells carrying such mutations could take over the culture," said Laurent.

Human pluripotent stem cells are cultured in several different ways. Key variables are the surfaces upon which the cells are cultured, called the substrate, and the methods used to transfer cells from one culture dish into another as they grow, called the passage method.

Originally, scientists determined that stem cells grew best when cultured atop of a "feeder" layer that included other types of cells, such as irradiated mouse embryonic fibroblasts. For reasons not fully understood, these cells provide stem cells with factors that support their growth. However, concerns about the feeder cells also introducing undesirable materials into stem cells has prompted development of feeder-free cultures.

Moving cells from one culture dish to another has traditionally been done manually, with technicians physically separating the cultured cells into small clumps with an instrument. "It's very labor-intensive," said Laurent, "so new methods that use enzymes to separate individual cells were created."

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Li Ka Shing Foundation renews support for Yale Stem Cell Center

By Stem Cell Medical Center

The Yale Stem Cell Center (YSCC), under the direction of biologist Haifan Lin, has announced a new generous grant of $1.86 million from the Li Ka Shing Foundation (LKSF), founded by Hong Kong businessman Li Ka-shing, to support education and healthcare initiatives. The contribution builds on a 2011 grant of $1.56 million to secure state-of-the-art equipment for stem cell research at Yale and includes new funding that will strengthen collaborations between Yale and Chinas Shantou University.

One of the fastest growing areas of biomedical science, stem cell research demands the very latest instrumentation and training. Since 2006, Lin has developed the Yale Stem Cell Center as both an incubator for scientific discovery and a training ground for new investigators.

The Yale Stem Cell Center offers a platform where both scientists and clinicians can ask important questions about stem cells and human health, Lin said. Continuing support from the Li Ka Shing Foundation will allow us to accelerate the pace and broaden the scope of our work.

Li said, Training side-by-side with leading scientists in stem cell research will be a transformative experience for the students and faculty at Shantou University Medical College, and I want to express my heart-felt appreciation to Professor Haifan Lin and the YSCC for this amazing opportunity.

Advances in stem cell science can offer basic insights into human development and the promise of new treatments for physical trauma, degenerative conditions, and genetic diseases. Because this research requires specialized instrumentation and expertise beyond what can be afforded by individual investigators, Lin has organized the Yale Stem Cell Center around four core laboratories that serve more than 80 Yale faculty members, along with researchers from other regional institutions.

In the Yale Stem Cell Center, Haifan Lin has developed an approach to collaborative research that truly serves as a model for universities and institutes around the country, said Robert J. Alpern, dean and the Ensign Professor at Yale School of Medicine. By sharing resources, laboratory techniques, and insights into how stem cells function, Haifan and his colleagues opened the door to discoveries that otherwise may not have been possible, for both basic science and clinical applications.

The new round of funding from LKSF will enable Yale investigators to purchase additional equipment to facilitate their research. This instrumentation will also support collaborations with scientists and clinicians in U.S. institutions such as the University of Connecticut Stem Cell Institute, the Massachusetts General Hospital Cancer Center, Albert Einstein College of Medicine, and St. Jude Childrens Research Hospital. Such exchanges can deepen our basic understanding of stem cell biology and help to translate todays technological breakthroughs into tomorrows personalized treatments and cures.

The grant also continues and expands the Yale Stem Cell Centers partnership with Shantou University, a key comprehensive university established through a public-private partnership between the Ministry of Education of Guangdong Province and the Li Ka Shing Foundation.

Yale is enormously grateful to Li Ka Shing Foundation for its continued support of basic science, translational research, and scholarly exchange, said Carolyn Slayman, Sterling Professor of Genetics, professor of cellular and molecular physiology, and deputy dean for academic & scientific affairs. This grant will help expedite the development of therapeutic treatments for some of the worlds most debilitating diseases.

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