Stem Cell Clinic

New single-cell analysis reveals complex variations in stem cells

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

4-Dec-2014

Contact: Kat J. McAlpine katherine.mcalpine@wyss.harvard.edu 617-432-8266 Wyss Institute for Biologically Inspired Engineering at Harvard @wyssinstitute

(BOSTON) -- Stem cells offer great potential in biomedical engineering due to their pluripotency, which is the ability to multiply indefinitely and also to differentiate and develop into any kind of the hundreds of different cells and bodily tissues. But the precise complexity of how stem cell development is regulated throughout states of cellular change has been difficult to pinpoint until now.

By using powerful new single-cell genetic profiling techniques, scientists at the Wyss Institute for Biologically Inspired Engineering and Boston Children's Hospital have uncovered far more variation in pluripotent stem cells than was previously appreciated. The findings, reported today in Nature, bring researchers closer to a day when many different kinds of stem cells could be leveraged for disease therapy and regenerative treatments.

"Stem cell colonies contain much variability between individual cells. This has been considered somewhat problematic for developing predictive approaches in stem cell engineering," said the study's co-senior author James Collins, Ph.D., who is a Wyss Institute Core Faculty member, the Henri Termeer Professor of Medical Engineering & Science at MIT, and a Professor of Biological Engineering at MIT. "Now, we have discovered that what was previously considered problematic variability could actually be beneficial to our ability to precisely control stem cells."

The research team has learned that there are many small fluctuations in the state of a stem cell's pluripotency that can influence which developmental path it will follow.

It's a very fundamental study but it highlights the wide range of states of pluripotency," said George Daley, study co-senior author, Director of Stem Cell Transplantation at Boston Children's Hospital and a Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. "We've captured a detailed molecular profile of the different states of stem cells."

Taking this into account, researchers are now better equipped to manipulate and precisely control which cell and tissue types will develop from an individual pluripotent stem cell or stem cell colony.

"The study was made possible through the use of novel technologies for studying individual cells, which were developed in part by collaborating groups at the Broad Institute, giving our team an unprecedented view of stem cell heterogeneity at the individual cell level," said Patrick Cahan, co-lead author on the study and Postdoctoral Fellow at Boston Children's Hospital and Harvard Medical School.

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New single-cell analysis reveals complex variations in stem cells

Predicting the storm: Can computer models improve stem cell transplantation?

By Uncategorized

PUBLIC RELEASE DATE:

4-Dec-2014

Contact: John Wallace wallacej@vcu.edu 804-628-1550 Virginia Commonwealth University @vcunews

Is the human immune system similar to the weather, a seemingly random yet dynamical system that can be modeled based on past conditions to predict future states? Scientists at VCU Massey Cancer Center's award-winning Bone Marrow Transplant (BMT) Program believe it is, and they recently published several studies that support the possibility of using next-generation DNA sequencing and mathematical modeling to not only understand the variability observed in clinical outcomes of stem cell transplantation, but also to provide a theoretical framework to make transplantation a possibility for more patients who do not have a related donor.

Despite efforts to match patients with genetically similar donors, it is still nearly impossible to predict whether a stem cell transplant recipient will develop potentially fatal graft-versus-host disease (GVHD), a condition where the donor's immune system attacks the recipient's body. Two studies recently published by the online journal Frontiers in Immunology explored data obtained from the whole exome sequencing of nine donor-recipient pairs (DRPs) and found that it could be possible to predict which patients are at greatest risk for developing GVHD and, therefore, in the future tailor immune suppression therapies to possibly improve clinical outcomes. The data provides evidence that the way a patient's immune system rebuilds itself following stem cell transplantation is representative of a dynamical system, a system in which the current state determines what future state will follow.

"The immune system seems chaotic, but that is because there are so many variables involved," says Amir Toor, M.D., member of the Developmental Therapeutics research program at Massey and associate professor in the Division of Hematology, Oncology and Palliative Care at the VCU School of Medicine. "We have found evidence of an underlying order. Using next-generation DNA sequencing technology, it may be possible to account for many of the molecular variables that eventually determine how well a donor's immune system will graft to a patient."

Toor's first study revealed a large and previously unmeasured potential for developing GVHD for which the conventional approach used for matching DRPs does not account. The conventional approach for donor-recipient compatibility determination uses human leucocyte antigen (HLA) testing. HLA refers to the genes that encode for proteins on the surface of cells that are responsible for regulating the immune system. HLA testing seeks to match DRPs who have similar HLA makeup.

Specifically, Toor and his colleagues used whole exome sequencing to examine variation in minor histocompatibility antigens (mHA) of transplant DRPs. These mHA are protein fragments presented on the HLA molecules, which are the receptors on cells' surface to which these fragments of degraded proteins from within a cell bind in order to promote an immune response. Using advanced computer-based analysis, the researchers examined potential interactions between the mHA and HLA and discovered a high level of mHA variation in HLA-matched DRPs that could potentially contribute to GVHD. These findings may help explain why many HLA-matched recipients experience GVHD, but why some HLA-mismatched recipients experience none remains a mystery. This seeming paradox is explained in a companion paper, also published in the journal Frontiers in Immunology. In this manuscript, the team suggests that by inhibiting peptide generation through immunosuppressive therapies in the earliest weeks following stem cell transplantation, antigen presentation to donor T cells could be diminished, which reduces the risk of GVHD as the recipients reconstitute their T-cell repertoire.

Following stem cell transplantation, a patient begins the process of rebuilding their T-cell repertoire. T cells are a family of immune system cells that keep the body healthy by identifying and launching attacks against pathogens such as bacteria, viruses or cancer. T cells have small receptors that recognize antigens. As they encounter foreign antigens, they create thousands of clones that can later be called upon to guard against the specific pathogen that presented the antigen. Over the course of a person's life, they will develop millions of these clonal families, which make up their T-cell repertoire and protect them against the many threats that exist in the environment.

This critical period where the patient rebuilds their immune system was the focus of the researchers' efforts. In previous research, Toor and his colleagues discovered a fractal pattern in the DNA of recipients' T-cell repertoires. Fractals are self-similar patterns that repeat themselves at every scale. Based on their data, the researchers believe that the presentation of minor histocompatability antigens following transplantation helps shape the development of T-cell clonal families. Thus, inhibiting this antigen presentation through immunosuppressive therapies in patients who have high mHA variation can potentially reduce the risk of GVHD by influencing the development of their T-cell repertoire. This is backed by data from clinical studies that show immune suppression soon after transplantation improves outcomes in unrelated DRPs.

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Predicting the storm: Can computer models improve stem cell transplantation?

Bone Marrow Stem Cell Treatment (BMAC) for Knee Osteoarthritis – Mayo Clinic – Video

By Stem Cell Treatment


Bone Marrow Stem Cell Treatment (BMAC) for Knee Osteoarthritis - Mayo Clinic
Shane Shapiro, M.D., orthopedic physician at Mayo Clinic in Florida, discusses a regenerative medicine clinical research trial to treat knee arthritis, which is the bone marrow stem cell treatment...

By: Mayo Clinic

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Bone Marrow Stem Cell Treatment (BMAC) for Knee Osteoarthritis - Mayo Clinic - Video

Research: NFL athletes are seeking unproven stem cell treatments

By Stem Cell Treatment

PUBLIC RELEASE DATE:

4-Dec-2014

Contact: David Ruth david@rice.edu 713-348-6327 Rice University @RiceUNews

Some National Football League (NFL) players have been seeking out unproven stem cell therapies to help accelerate recoveries from injuries, according to a new paper from Rice University's Baker Institute for Public Policy. While most players seem to receive treatment within the United States, several have traveled abroad for therapies unavailable domestically and may be unaware of the risks involved, the paper found.

The paper is published in the 2014 World Stem Cell Report, which is a special supplement to the journal Stem Cells and Development and is the official publication of the 2014 World Stem Cell Summit being held Dec. 3-5 in San Antonio.

"With the rise of new and unproven stem cell treatments, the NFL faces a daunting task of trying to better understand and regulate the use of these therapies in order to protect the health of its players," said Kirstin Matthews, the Baker Institute fellow in science and technology policy and an expert on ethical and policy issues related to biomedical research and development. She co-authored the paper with Maude Rowland Cuchiara, the Baker Institute scholar for science and technology policy.

Each year, more than 700 stem cell clinics around the world open their doors to "stem cell tourists," according to the paper's authors. Patients travel abroad to seek treatment for ailments -- ranging from autism to multiple sclerosis and paralysis -- for which no cure exists and treatment options are limited. The use of stem cells as orthopedic therapies in the U.S. is becoming more commonplace and has drawn the attention of elite athletes, most notably NFL players, who have been vocal about receiving stem cell treatments and their successful recoveries. The paper notes that 12 NFL players have been identified publicly as having received an unapproved stem cell treatment since 2009.

"The online data on NFL players and the clinics where they obtained treatment suggest that players may be unaware of the risks they are taking," Matthews said. "Furthermore, players who are official spokespersons for these clinics could influence others to view the therapies as safe and effective despite the lack of scientific research to support these claims."

The paper notes that while unproven stem cell treatments in U.S.-based clinics rarely have severe side effects, they also arguably have little to no appreciable therapeutic benefits. The paper focuses on treatments unapproved by the U.S. Food and Drug Administration and undertaken by NFL players in the past five years. The authors highlight the types of treatments obtained and how the clinics advertise specifically to athletes. They also review the intended and unintended consequences of high-profile players receiving and advocating for these types of therapies.

The authors suggest the NFL and other sports leagues should review the procedures for stem cell treatment to determine how best to support, evaluate and possibly regulate stem cell treatments to ensure the safety of their players and their followers. "This could be organized similarly to the NFL investigations on the effects of concussions and traumatic brain injuries," Matthews said.

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Research: NFL athletes are seeking unproven stem cell treatments

Approved breast cancer drug offers hope for the treatment of blood disorders

By Stem Cell Treatment

PUBLIC RELEASE DATE:

4-Dec-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press @CellPressNews

Blood cancers are more common in men than in women, but it has not been clear why this is the case. A study published by Cell Press December 4th in Cell Stem Cell provides an explanation, revealing that female sex hormones called estrogens regulate the survival, proliferation, and self-renewal of stem cells that give rise to blood cancers. Moreover, findings in mice with blood neoplasms--the excessive production of certain blood cells--suggest that a drug called tamoxifen, which targets estrogen receptors and is approved for the treatment of breast cancer, may also be a valuable strategy for blocking the development of blood neoplasms in humans.

"Our study demonstrates that targeting estrogen signaling with a clinically approved drug, at doses with an acceptable toxicity profile in humans, provides a novel potential therapeutic strategy for a set of neoplasms currently without a definitive cure," said senior study author Simn Mndez-Ferrer of the National Center for Cardiovascular Research (CNIC) in Madrid, Spain.

Myeloproliferative neoplasms cause large numbers of abnormal white blood cells to be produced and enter the bloodstream, potentially causing life-threatening symptoms. These diseases can lead to cancer and arise from blood cells called hematopoietic stem/progenitor cells (HSPCs), which give rise to all of the other blood cells. Leukemia and other blood cancers are more common in men than in women, strongly suggesting that sex hormones such as estrogens contribute to the development of these malignancies. But until now, it has not been clear whether estrogen signaling could directly control normal and cancerous HSPCs.

In the new study, Mndez-Ferrer and Abel Snchez-Aguilera of CNIC found that HSPCs express estrogen receptors, and activation of these receptors with tamoxifen affected the survival, proliferation, and self-renewal of these cells. In mice with a genetic mutation associated with blood neoplasms, tamoxifen treatment blocked the excessive production of blood cells by restoring normal levels of programmed cell death in mutant cells. Moreover, tamoxifen enhanced the effects of conventional chemotherapy on cancerous cells in a mouse model of leukemia.

"Our results suggest that tamoxifen, at a similar dose used for the treatment of other diseases, might be useful to treat myeloproliferative neoplasms at various stages, without being toxic to normal blood cells," Mndez-Ferrer says. "The fact that this drug is FDA-approved, readily available and sufficiently safe facilitates the potential translation of our results from the bench to the bedside."

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Cell Stem Cell, Sanchez-Aguilera et al.: "Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis"

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Approved breast cancer drug offers hope for the treatment of blood disorders

Not all induced pluripotent stem cells are made equal: McMaster researchers

By Stem Cell Medicine

PUBLIC RELEASE DATE:

3-Dec-2014

Contact: Veronica McGuire vmcguir@mcmaster.ca 90-552-591-402-2169 McMaster University @mcmasteru

Hamilton, ON (Dec. 3, 2014) - Scientists at McMaster University have discovered that human stem cells made from adult donor cells "remember" where they came from and that's what they prefer to become again.

This means the type of cell obtained from an individual patient to make pluripotent stem cells, determines what can be best done with them. For example, to repair the lung of a patient with lung disease, it is best to start off with a lung cell to make the therapeutic stem cells to treat the disease, or a breast cell for the regeneration of tissue for breast cancer patients.

Pluripotency is the ability stem cells have to turn into any one of the 226 cell types that make up the human body.The work challenges the previously accepted thought that any pluripotent human stem cell could be used to similarly to generate the same amount of mature tissue cells.

This finding, published today in the prestigious science journal Nature Communications, will be used to further drug development at McMaster, and potentially improve transplants using human stem cell sources.

The study was led by Mick Bhatia, director of the McMaster Stem Cell and Cancer Research Institute. He holds the Canada Research Chair in Human Stem Cell Biology and he is a professor in the Department of Biochemistry and Biomedical Sciences of the Michael G. DeGroote School of Medicine.

"It's like the stem cell we make wants to become a doctor like its grandpa or an artist like its great-grandma," said Bhatia.

"We've shown that human induced pluripotent stem cells, called iPSCs, have a memory that is engraved at the molecular/genetic level of the cell type used to make them, which increases their ability to differentiate to the parent tissue type after being put in various stem cell states.

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Not all induced pluripotent stem cells are made equal: McMaster researchers

Not All Induced Pluripotent Stem Cells Are Made Equal

By Stem Cell Medicine

Released: 1-Dec-2014 1:00 PM EST Embargo expired: 3-Dec-2014 5:00 AM EST Source Newsroom: McMaster University Contact Information

Available for logged-in reporters only

Newswise Hamilton, ON (Dec. 3, 2014) Scientists at McMaster University have discovered that human stem cells made from adult donor cells remember where they came from and thats what they prefer to become again.

This means the type of cell obtained from an individual patient to make pluripotent stem cells, determines what can be best done with them. For example, to repair the lung of a patient with lung disease, it is best to start off with a lung cell to make the therapeutic stem cells to treat the disease, or a breast cell for the regeneration of tissue for breast cancer patients.

Pluripotency is the ability stem cells have to turn into any one of the 226 cell types that make up the human body.The work challenges the previously accepted thought that any pluripotent human stem cell could be used to similarly to generate the same amount of mature tissue cells.

This finding, published today in the prestigious science journal Nature Communications, will be used to further drug development at McMaster, and potentially improve transplants using human stem cell sources.

The study was led by Mick Bhatia, director of the McMaster Stem Cell and Cancer Research Institute. He holds the Canada Research Chair in Human Stem Cell Biology and he is a professor in the Department of Biochemistry and Biomedical Sciences of the Michael G. DeGroote School of Medicine.

Its like the stem cell we make wants to become a doctor like its grandpa or an artist like its great-grandma, said Bhatia.

Weve shown that human induced pluripotent stem cells, called iPSCs, have a memory that is engraved at the molecular/genetic level of the cell type used to make them, which increases their ability to differentiate to the parent tissue type after being put in various stem cell states.

So, not all human iPSCs are made equal, Bhatia added. Moving forward, this means that iPSC generation from a specific tissue requiring regeneration is a better approach for future cellular therapies. Besides being faster and more cost-efficient in the development of stem cell therapy treatments, this provides a new opportunity for use of iPSCs in disease modeling and personalized drug discovery that was not appreciated before.

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Not All Induced Pluripotent Stem Cells Are Made Equal

Researchers recreate stem cells from deceased patients to study present-day illnesses

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

1-Dec-2014

Contact: Cara Martinez cara.martinez@cshs.org 310-423-7798 Cedars-Sinai Medical Center @cedarssinai

LOS ANGELES (Dec. 1, 2014) - Research scientists have developed a novel method to re-create brain and intestinal stem cells from patients who died decades ago, using DNA from stored blood samples to study the potential causes of debilitating illnesses such as inflammatory bowel disease.

The lab research, published in the journal STEM CELLS Translational Medicine, could yield new therapies for people who suffer from aggressive motor-neuron and gut-related conditions that proved fatal to the deceased patients who long-ago volunteered their blood samples.

"The potential implications of this research are vast," said Dhruv Sareen, PhD, the study's lead author, and assistant professor and director of the David and Janet Polak Foundation Stem Cell Core Laboratory in the Board of Governors Regenerative Medicine Institute.

By using a deceased patient's stored blood samples, Sareen and his colleagues found that they can develop stem cells known as iPSCs in a petri dish - essentially reanimating diseased cells from patients long after they have died.

This approach allows researchers to connect the dots between a deceased patient's symptoms, genetic information contained in DNA and the behavior of stem cells in the lab. This, in turn, enables investigators to study the biological mechanisms behind diseases and potentially design new therapies.

The technique also allows physicians to replace invasive biopsy procedures typically required of living patients to create iPSC cells.

"These novel developments allow us to create new lines of stem cells from literally millions of patient samples stored in large repositories," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute. "Some of these deceased patients were diagnosed with rare and important diseases."

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Researchers recreate stem cells from deceased patients to study present-day illnesses

World Stem Cell Summit kicks off in SA with Public Education Day

By Stem Cell Medical Center

NEWS

1200+ scientists, patient advocates from 40 countries in town for summit

Posted YESTERDAY, 6:04 PM Updated YESTERDAY, 6:33 PM

SAN ANTONIO - More than a thousand scientists, industry leaders and patient advocates from 40 countries are headed to San Antonio for the World Stem Cell Summit.

Organizers are calling it the center of the universe when it comes to stem cells and regenerative medicine.

On Tuesday the summit kicked off with Public Education Day, where some of the smartest scientists in the field broke the topic down into bite-sized pieces.

"To be able to replenish our cells that die within a tissue on a daily basis, in order for us to be able to heal wounds, we have to have stem cells," said Elaine Fuchs, an investigator for the Howard Hughes Medical Institute.

She started her research in the field in the 1970s with work on skin stem cells, and said she was fascinated with creating skin in a petri dish that could then be used for burn therapy.

Fuchs spoke at Public Education Day about the most basic biology of stem cells and said that knowledge is leading to a new world in medicine.

"The biology of stem cells is gong to be and is being extremely valuable in terms of developing new therapies and coming up with new drugs to treat various different devastating diseases," Fuchs said.

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World Stem Cell Summit kicks off in SA with Public Education Day

The Miami Stem Cell Treatment Center Announces Adult Stem Cell Public Seminars in Baco Raton and Fort Lauderdale …

By Stem Cell Treatment

Fort Lauderdale and Boca Raton, Florida (PRWEB) December 02, 2014

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

The seminars will be held on Sunday, December 7, 2014, at 1:00pm and 3:00pm at the Miami Stem Cell Treatment Center, 1515 N. Federal Highway, Suite 105, Boca Raton, FL 33432 and Thursday, December 11, 2014 at 2:00 pm at the Thasos Greek Taverna, 3330 E. Oakland Park Blvd, Ft. Lauderdale, FL 33308. Please RSVP at (561) 331-2999.

The Miami Stem Cell Treatment Center abides by 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 body's natural healing cells - they are recruited by chemical signals emitted by damaged tissues to repair and regenerate the bodys injured cells. The Miami Stem Cell Treatment Center only uses Adult Autologous Stem Cells from a persons own fat No embryonic stem cells are used. Current areas of study include: Emphysema, COPD, Asthma, Heart Failure, Parkinsons Disease, Stroke, Multiple Sclerosis, Lupus, Rheumatoid Arthritis, Crohns Disease, and degenerative orthopedic joint conditions. For more information, or if someone thinks they may be a candidate for one of the adult stem cell protocols offered by the Miami Stem Cell Treatment Center, they may contact Dr. Gionis directly at (561) 331-2999, or see a complete list of the Centers study areas at: http://www.MiamiStemCellsUSA.com.

About the Miami Stem Cell Treatment Center: The Miami Stem Cell Treatment Center is an affiliate of the Cell Surgical Network (CSN); they are located in Baco Raton, Orlando, and Miami, Florida. 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 Miami 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; and the study is registered with Clinicaltrials.gov, a service of the U.S. National Institutes of Health (NIH). For more information visit our website: http://www.MiamiStemCellsUSA.com.

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The Miami Stem Cell Treatment Center Announces Adult Stem Cell Public Seminars in Baco Raton and Fort Lauderdale ...

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