Category Archives: Pennsylvania Stem Cells

RICHMOND, Calif., Oct. 16, 2014 /PRNewswire/ --Sangamo BioSciences, Inc. (NASDAQ: SGMO) announced that Company scientists and clinicians, as well as academic collaborators, were invited speakers at three major scientific meetings in Europe and the United States. Their presentations covered a number of therapeutic uses of Sangamo's novel zinc finger protein (ZFP) technology, but were primarily focused on reviewing the progress of the Company's ZFP Therapeutic program in HIV/AIDS. Presentations included a review of current clinical data with SB-728-T as well as the design of Sangamo's ongoing Phase 2 clinical trial (SB-728-mR-1401) and the preclinical rationale for targeting CCR5 in hematopoietic stem cells, which is expected to enter clinical testing in late 2014.

"Participation in these key scientific forumsthe NIH 'Strategies for an HIV Cure 2014' meeting, the European Society of Gene and Cell Therapy (ESGCT) Annual Meeting, and most recently, the British HIV Association (BHIVA) Autumn Conferenceunderscores the tremendous interest from the international scientific and clinical communities in Sangamo's progresstoward developing a ZFP Therapeutic that may replicate natural, durable resistance to HIV infection," said Edward Lanphier, Sangamo's president and CEO. "Sangamo's ongoing Phase 2 trial incorporates all that we have learned from previous trials about the potential mechanism of this novel therapeutic clinical approach, and we believe the data produced will provide a clear path to pivotal studies. We expect to accrue all subjects onto the clinical trial by the end of 2014 and to present data in 2015."

This week, October 15-17, at the "Strategies for an HIV Cure 2014" conference organized by the National Institute for Allergies and Infectious Diseases at the NIH, Philip Gregory, D.Phil., Sangamo's senior vice president, research, and CSO, will present an overview of the SB-728-T program, along with Sangamo collaborators Paula Cannon, Ph.D., Associate Professor Molecular Microbiology & Immunology, Pediatrics, Biochemistry & Molecular Biology, Keck School of Medicine, University of Southern California; Pablo Tebas, M.D., Professor of Medicine at the Hospital of the University of Pennsylvania; and Hans-Peter Kiem, M.D., Jose Carreras/E. Donnall Thomas Endowed Chair for Cancer Research at the Fred Hutchinson Cancer Research Center.

Dr. Gregory will also be presenting an overview of the SB-728-T clinical program at a "bench to bedside" discussion forum of the annual ESGCT meeting, October 23-26, which will beheld in The Hague. Dr. Gregory and Sangamo collaborator Luigi Naldini, M.D., Ph.D., Director, San Raffaele Telethon Institute for Gene Therapy (TIGET) will discuss the larger field of genome editing, utilizing the company's HIV studies as a model. Sangamo collaborators will also be discussing the use of Sangamo zinc finger nucleases in preclinical and research studies of SCID-X1, cancer and Wiskott-Aldrich Syndrome.

Earlier in October, Geoffrey Nichol, M.B., Ch.B., Sangamo's executive vice president, research and development, was invited to deliver the Foundation Lecture, reviewing recent clinical data from the SB-728-T program at the Autumn Conference of the British HIV Association which was held in London, UK.

Sangamo's SB-728-mR-1401 trial is an open-label, multi-center study designed primarily to evaluate safety and tolerability and the effect of repeat doses of SB-728-T following optimal cyclophosphamide (Cytoxan) pre-conditioning, on engraftment, viral load and total CD4 counts in peripheral blood. Electroporation of mRNA is being used to deliver the zinc finger nucleases to a subject's T-cellsto generate the modified autologous T-cell product (SB-728-T). mRNA delivery is more efficient than the previous adenoviral delivery method used and enables treatment of subjects with multiple doses of CCR5-modified cells. Up to nine subjects will be enrolled into two cohorts. Each subject will receive a total of up to 40 billion ZFN modified T-cells. The first cohort will receive this dose divided into infusions of two equal doses of SB-728mR-T 14 days apart after a cyclophosphamide (1 g/m2) preconditioning treatment two days prior to the first SB-728mR-T infusion, and the second cohort will receive three doses of cells. Dividing the total cell dose and administering sequentially in this manner is thought to maximize overall cell engraftment. Four weeks after the last SB-728-mR infusion, subjects with CD4 cell counts 500 cells/mm3 will undergo a 16 week treatment interruption (TI) during which time their anti-retroviral therapy will be discontinued.

About SB-728-TSangamo's therapy, SB-728-T, is generated by ZFN-mediated modification of the gene encoding CCR5 in a patient's own T-cells.ZFN modification disrupts the expression of this key co-receptor for HIV entry and renders cells resistant to HIV infection. The approach is based on the observation that a naturally occurring mutation in the CCR5 gene, CCR5 delta-32, provides protection from HIV infection. Individuals in whom both copies of the CCR5 gene carry the delta-32 mutation are generally not susceptible to the most common strain of HIV.

About SangamoSangamo BioSciences, Inc. is focused on Engineering Genetic Cures for monogenic and infectious diseases by deploying its novel DNA-binding protein technology platform in therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic for the treatment of HIV/AIDS (SB-728-T) and NGF-AAV for Alzheimer's disease (CERE-110). Sangamo's other therapeutic programs are focused on monogenic and rare diseases. The Company has formed a strategic collaboration with Shire International GmbH to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases, and with Biogen Idec for hemoglobinopathies, such as sickle cell disease and beta-thalassemia. It has also established strategic partnerships with companies in non-therapeutic applications of its technology, including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the Company's website at http://www.sangamo.com.

ZFP Therapeutic is a registered trademark of Sangamo BioSciences, Inc.

This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references relating to research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform for the treatment of HIV/AIDS, including a potential functional cure or control for HIV/AIDS, the ability of a ZFP Therapeutic to control HIV infection, the initiation of clinical studies and enrollment of aPhase 2 clinical trial for HIV/AIDS, projected timing of release of SB-728-T clinical data, clinical data from new HIV/AIDS trials to support pivotal studies, the efficiency of the mRNA delivery system, and the use of Sangamo's technology in potential preclinical and research studies. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo's public filings with the Securities and Exchange Commissio
n, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.

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Sangamo BioSciences ZFP Therapeutic Program in HIV/AIDS Featured at Three Major Scientific Conferences in October 2014

Stem Cell Therapy PennsylvaniaWorldstemcells.comis one of the leadingstem cell therapy and treatmentproviders for residents ofPennsylvaniaand across the nation. Our cutting edge technology and compassionate staff truly set us apart from the competition. We are a US based company that understands your needs and concerns when looking for a stem cell treatment center. Our treatment center is located in Cancun, Mexico.

Getting Started With Your Stem CellTherapy and Treatments Here at World Stem Cells LLC we try to make the process ofreceiving stem cell transplantsas easy as possible. We will help you figure out what your needs are and help you reach your goals as fast as possible. Follow the steps below on what to do.

Option 1 1.) Go to any page on our website and fill out the contact form. 2.) Fill in the required information and select the condition you would like to treat with stem cell therapy. 3.) Be sure to include any special information in the comments section. 4.)Click the submit button and we will contact you in a timely manner. 5.) Thats it, youre done!!!

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Stem Cell Therapy Pennsylvania | Stem Cell Treatments

PUBLIC RELEASE DATE:

15-Oct-2014

Holly Auer Penn Medicine 215-349-5659 215-200-2313 holly.auer@uphs.upenn.edu

Rachel Salis-Silverman Children's Hospital of Philadelphia 267-426-6063 267-970-3685 Salis@email.chop.edu

PHILADELPHIA Ninety percent of children and adults with acute lymphoblastic leukemia (ALL) who had relapsed multiple times or failed to respond to standard therapies went into remission after receiving an investigational personalized cellular therapy, CTL019, developed at the Perelman School of Medicine at the University of Pennsylvania. The results are published this week in The New England Journal of Medicine.

The new data, which builds on preliminary findings presented at the American Society of Hematology's annual meeting in December 2013, include results from the first 25 children and young adults (ages 5 to 22) treated at the Children's Hospital of Philadelphia and first five adults (ages 26 to 60) treated at the Hospital of the University of Pennsylvania. Twenty-seven of the 30 patients in the studies achieved a complete remission after receiving an infusion of these engineered "hunter" cells, and 78 percent of the patients were alive six months after treatment.

"The patients who participated in these trials had relapsed as many as four times, including 60 percent whose cancers came back even after stem cell transplants. Their cancers were so aggressive they had no treatment options left," said the study's senior author, Stephan Grupp, MD, PhD, a professor of Pediatrics in Penn's Perelman School of Medicine and director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. "The durable responses we have observed with CTL019 therapy are unprecedented."

Shannon Maude, MD, PhD, an assistant professor of Pediatrics and a pediatric oncologist at CHOP, and Noelle Frey, MD, MSCE, an assistant professor of Medicine and an oncologist at Penn's Abramson's Cancer Center, are co-first authors of the new study. The research team is led by Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in the Abramson Cancer Center, along with David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in the Abramson Cancer Center.

CTL019 manufacturing begins with a patient's own T cells, which are collected via an apheresis process similar to blood donation, then reprogrammed in Penn's Clinical Cell and Vaccine Production Facility with a gene transfer technique that teaches the T cells to target and kill tumor cells. The engineered cells contain an antibody-like protein known as a chimeric antigen receptor (CAR), which is designed to bind to a protein called CD19 found on the surface of B cells, including the cancerous B cells that characterize several types of leukemia. The modified "hunter" cells are then infused back into the patient's body, where they both multiply and attack the cancer cells. A signaling domain built into the CAR promotes rapid multiplication of the "hunter" cells, building an army of tumor-killing cells that tests reveal can grow to more than 10,000 new cells for each single engineered cell patients receive.

Nineteen patients in the study remain in remission, 15 with this therapy alone, including a 9 year old who was the first ALL patient to receive the therapy more than two years ago. The follow-up periods reported in the study are more than six months for most patients, with a range from 1.4 to 24 months. Five patients went off-study for alternate therapy, three of whom proceeded to allogeneic stem cell transplants while in remission. Seven patients relapsed, between 6 weeks and 8.5 months after their infusions, including three whose cancers returned as CD19-negative leukemia that would not have been targeted by the modified cells.

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Personalized cellular therapy achieves complete remission in 90 percent of acute lymphoblastic leukemia patients studied

God alone is the Lord of life from its beginning until its end; no one can under any circumstance claim the right directly to destroy an innocent human being.

(Catechism of the Catholic Church 2258)

Medical science today holds out the promise of cures to diseases and medical advances far beyond anything imagined, even a generation ago. Much of what we hear, particularly in media accounts of this type of medical miracle, has to do with a remarkable technology called stem cell research. This new medical research industry currently treats numerous illnesses and injuries and offers hope for more cures using adult stem cells.

We rejoice with these advances in medical science and the promise of relief to human suffering. At the same time, we have an obligation to ensure that medical capabilities do not progress so rapidly that they lack an ethical and moral foundation. Whatever is accomplished, we must be sure that it is not just what we are able to do but what we should do. There is a definite and necessary moral context for medical development as well as an ethical content to decisions involving stem cell research. It is this moral dimension of medical science that we call to your attention.

As the Bishops of Pennsylvania, we have a responsibility to help people make an informed moral judgment about one of the most important issues that we, as a people, face today. We must examine carefully the facts to determine what exactly is at issue and why the moral prohibition against the use of evil means to achieve a good end is applicable.

What is a stem cell? A stem cell is an unspecialized cell. Stem cells have the potential to develop into a full range of tissues that constitute the human body. This makes them so attractive to researchers. The science of cell therapy concentrates on ways to replace, repair or enhance the biological function of damaged tissues or organs in the body.

What are embryonic stem cells? At the very beginning of human life, the sperm and egg come together to form an embryo. After that embryo has grown for about 5-7 days, it contains embryonic stem cells which can be extracted. In this procedure, the embryo is killed. Similar embryonic-type stem cells can also be obtained from aborted fetuses. The extracted cells are then cultivated in a laboratory, replicating over and over again.

What are adult stem cells and from where do they come? Fortunately, embryos are not the only source of stem cells. Adult stem cells are found in the individual at any time after birth. There are a number of ethical sources of stem cells that hold out realistic hope for cures and treatments of diseases. Stem cells from adult tissues, which are committed to differentiating into a limited number of cell types such as liver, brain or blood, are called adult stem cells. These too have the capability of developing into specific tissues. Adult-type stem cells can also be derived from various pregnancy-related sources such as umbilical cords, placentas and amniotic fluid. Some scientists today assert that not only are adult stem cells more readily available but they are also more effective in treating diseases.

Which of the types of stem cells are medically most successful? Stem cells derived from placental or umbilical cord blood have proven to be remarkably effective, similar to other adult stem cells. Originally it was theorized that stem cells from these various sources would be ineffective because they are limited in their ability to become various types of cells. However, alternative sources of stem cells have been successfully differentiated into needed tissue and are already effective in healing human illnesses. More than 50 diseases have already been treated successfully in humans using adult and umbilical cord stem cells.

What does the Church teach about adult stem cell research? The Church does not oppose all stem cell research. In fact, the Church encourages and supports medical development and technological advancement. Adult stem cells are a solution. These cells exist in our bodies and provide a natural repair mechanism for many tissues of our bodies. There are methods available for obtaining human stem cells from adults. Furthermore, many therapies in humans have been successfully developed using adult stem cells. These include treatments for leukemia, juvenile diabetes, spinal cord injury, immune deficiency and corneal damage. It is important to note that no therapies in humans have ever been successfully carried out using embryonic stem cells.

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Questions and Answers on Stem Cell Research | Pennsylvania ...

Philadelphia PA Stem Cell Research is a complex and beneficial science using stem cells in a lab environment to better understand how normal human development works, and also to look for and develop new treatments for a wide range of human ailments. Philadelphia Pennsylvania Stem Cell Research involves two types of stem cells, classified as either embryonic stem cells or adult stem cells, which are used according to the type of Philadelphia PA Stem Cell Research that is desired.

Embryonic stem cells are derived from pre-embryos, called blstocysts, approximately three to five days old. They are created specifically for fertilization treatments in the Philadelphia Pennsylvania Stem Cell Research lab, will not be used to start a pregnancy, and will be discarded if not used for research. Doctors use in-vitro fertilization to create an embryo in a culture dish, which after three to five days becomes a blstocysts. Philadelphia PA Stem Cell Research lab technicians then extract the inner cell mass from the blstocysts, which is used to derive embryonic stem cells in the Philadelphia Pennsylvania Stem Cell Research facility.Embryonic stem cells are classified as pluripotent.

This means they can develop into any type of cell in a fully developed human body. It should be noted that embryonic stem cells cant develop into placenta or umbilical cord tissues, but they do appear to be able to develop into any other type of cell in a human body. What is so important about embryonic Philadelphia PA Stem Cell Research is that it enables very flexible research, as the stem cells can be grown into any type of cell needing to be researched, at any time, at the Philadelphia Pennsylvania Stem Cell Research facility. This makes for more efficient and more productive stem call research, promising a faster path to cures for ailments that devastate humanity. Philadelphia PA Stem Cell Research cannot use adult stem cells to generate just any desired tissues since they are already programmed. They are quite useful nonetheless, and Philadelphia Pennsylvania Stem Cell Research doctors have identified caches of adult stem cells in several tissues of the human body.

Philadelphia PA Stem Cell Research in general has been able to make some wonderful advancement and create excellent treatments using adult stem cells. But there are limitations to doing Philadelphia Pennsylvania Stem Cell Research using "only" adult stem cells. Adult stem cells are able to give rise to related kinds of cells in their home tissues, but for example Kidney stem cells cannot generate heart cells, and liver stem cells cannot generate brain cells.

A great deal of Philadelphia PA Stem Cell Research remains to be done, and at this point Philadelphia Pennsylvania Stem Cell Research doctors have developed a technique for getting an adult stem cell to behave similar to an embryonic stem cell. This specialized Philadelphia PA Stem Cell Research technique creates what are called induced pluripotent stem cells (iPS). They can be produced from adult cells in skin, fatty tissue, and other sources. With this, Philadelphia Pennsylvania Stem Cell Research remains a promising field. There is of course a great deal more work to do, but Philadelphia PA Stem Cell Research promises to benefit mankind in many profound ways.

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Philadelphia Pennsylvania Stem Cell Research ...

A postdoctoral position is available immediately in the area of cancer and stem cell biology at the Perelman School of Medicine and Abramson Cancer Center of the University of Pennsylvania. The position is in the laboratory of Dr. Dev Basu in the Division of Head and Neck Surgery. Postdoctoral training and career development will be supported by close affiliation with the lab of Dr. Anil Rustgi, Chief of the Division of Gastroenterology. Dr. Rustgi leads a well-established, NCI P01-funded program in squamous cell carcinoma biology and will provide senior level mentorship for the position. Candidates are sought to join a rapidly growing translational research program focusing on oral squamous cell carcinomas. Studies will be supported by two new NIH/NIDCR grants as well as industry-sponsored collaborations. This program aims to develop novel approaches to targeting the tumor cell subpopulations within oral cancer that are innately resistant to current therapies. Studies will emphasize rigorous molecular and functional definition of stem cell-like subpopulations and pursue detailed understanding of signaling mechanisms involved in their homeostasis. Work will rely upon our labs experience in 3-dimensional in vitro cancer models and in vivo xenografts, in addition to heavily utilizing patient-derived tumor specimens. Significant prior training in stem cell biology, epigenetics, cancer biology, cell biology, or biochemistry is strongly desirable. Interested individuals should send cover letter, CV, and reference information by e-mail to:

Devraj Basu, M.D, Ph.D., F.A.C.S. Assistant Professor Dept. Otorhinolaryngology-Head & Neck Surgery The University of Pennsylvania 3600 Spruce St., 5 Ravdin/Silverstein Philadelphia, PA 19104

email: devraj.basu@uphs.upenn.edu

website: http://www.med.upenn.edu/apps/faculty/index.php/g275/p8137952 Rustgi lab website: http://www.med.upenn.edu/apps/faculty/index.php/g20000220/p543

Don't forget to mention Naturejobs when applying.

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Postdoctoral Fellow, Cancer and Stem Cell Biology ...

Bloodless Stem Cell Transplant Program

Stem cell transplant (formerly known as bone marrow transplant) is a procedure that replaces destroyed cells as a result of high dose chemotherapy including bone marrow cells with healthy cells or stem cells. Patients diagnosed with lymphoma, leukemia or multiple myeloma often undergo this procedure. Patients seeking a bloodless approach to stem cell transplant have this option at Pennsylvania Hospitals Center for Bloodless Medicine and Surgery.

The Bloodless Stem Cell Transplant Program at Pennsylvania Hospital is unique and the first of its kind. If you are a patient requiring bloodless stem cell transplantation, consider that physicians from The Center for Bloodless Medicine and Surgery at Pennsylvania Hospital:

Patients undergoing bloodless stem cell transplants at our Center follow a strict regimen of iron and eythropoietin (EPO) treatments to increase hemoglobin levels. After the chemotherapy treatments, our team closely monitors our patients to increase platelet counts. Since patients and their families need to be close to our hospital during this time, we offer constant staff support to assist with accommodations, transportation and other daily necessities.

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Bloodless Stem Cell Transplant Program at Pennsylvania ...

By expanding the use of adipose tissue and its stem cell components, scientist and surgeons have made significant strides in aesthetic and reconstructive surgery. The opportunities for regenerative medicine interventions based on adult stem cells are tremendous IvonaPercec, MD, PhD

As researchers work on reconfiguring cells to take on new regenerative properties, a new review from Penn Medicine plastic surgeons sheds additional light on the potential power of adipose-derived stem cells or adult stem cells harvested from fatty tissue in reconstructive and regenerative medicine.

Fat-derived stem cells hold potential for regenerative medicine November 9, 2012 in Surgery (Medical Xpress)As researchers work on reconfiguring cells to take on new regenerative properties, a new review from Penn Medicine plastic surgeons sheds additional light on the potential power of adipose-derived stem cells or adult stem cells harvested from fatty tissue in reconstructive and regenerative medicine.

Reconstructive plastic surgeons have clinically integrated fat grafting into different surgeries for years, for breast, facial, and other reconstructive and restorative surgeries, with good success. Now, researchers are beginning to understand the power that fatty tissue holds. This new paper, published in the Aesthetic Surgery Journal, enforces that adipose-derived stem cells can be routinely isolated from patients, and once molecular methods are worked out, may be useful for a multitude of regenerative medicine applications. The opportunities for regenerative medicine interventions based on adult stem cells are tremendous. It is critically important for us to better understand the biology of these cells so that we can develop novel, safe and effective treatments for our patients using their own cells. said the papers senior author, IvonaPercec, MD, PhD, assistant professor in the division of Plastic Surgery in the Perelman School of Medicine at the University of Pennsylvania.

Many groups are looking into different modes of isolating and modifying these cells for their regenerative properties, including experts at Penns Institute for Regenerative Medicine and around Penn Medicine. For example, Dr. Percecs team is conducting translational research into the mechanisms controlling adipose-derived stem cells, and how they contribute to the normal human aging process. Stem cells can undergo multiple divisions without differentiation, making them useful tools for cell-replacement therapy. Embryonic stem cells can convert to any cell type, whereas adult stem cells, like the stem cells derived from fat, can differentiate into many, but not all, cell types. A persons own fat tissue could then potentially be converted into cells specially designed to repair damage to the heart, cartilage, blood vessels, brain, muscle, or bone. As regenerative medicine techniques are refined, experts will continue to explore the utility and benefits of stem cells derived from adipose tissue.

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University of Pennsylvania | The Stem Cell Blog

PHILADELPHIA - Researchers at the University of Pennsylvania School of Medicine have devised a totally new and far more efficient way of generating induced pluripotent stem cells (iPSCs), immature cells that are able to develop into several different types of cells or tissues in the body. The researchers used fibroblast cells, which are easily obtained from skin biopsies, and could be used to generate patient-specific iPSCs for drug screening and tissue regeneration.

iPSCs are typically generated from adult non-reproductive cells by expressing four different genes called transcription factors. The generation of iPSCs was first reported in 2006 by Shinya Yamanaka, and multiple groups have since reported the ability to generate these cells using some variations on the same four transcription factors.

The promise of this line of research is to one day efficiently generate patient-specific stem cells in order to study human disease as well as create a cellular "storehouse" to regenerate a person's own cells, for example heart or liver cells.Despite this promise, generation of iPSCs is hampered by low efficiency, especially when using human cells.

"It's a game changer," says Edward Morrisey, PhD, professor in the Departments of Medicine and Cell and Developmental Biology and Scientific Director at the Penn Institute for Regenerative Medicine. This is the first time we've been able to make induced pluripotent stem cells without the four transcription factors and increase the efficiency by 100-fold. Morrisey led the study published this week in Cell Stem Cell.

Generating induced pluripotent stem cells efficiently is paramount for their potential therapeutic use, noted James Kiley, PhD, director of the National Heart, Lung, and Blood Institutes Division of Lung Diseases. This novel study is an important step forward in that direction and it will also advance research on stem cell biology in general.

Before this procedure, which uses microRNAs instead of the four key transcription factor genes, for every 100,000 adult cells re-programmed, researchers were able to get a small handful of iPSCs, usually less than 20. Using the microRNA-mediated method, they have been able to generate approximately 10,000 induced pluripotent stem cells from every 100,000 adult human cells that they start with. MicroRNAs (miRNAs) are short RNA molecules that bind to complementary sequences on messenger RNAs to silence gene expression.

The Morrisey lab discovered this new approach through studies focusing on the role of microRNAs in lung development. This lab was working on a microRNA cluster called miR302/367, which plays an important role in lung endoderm progenitor development. This same microRNA cluster was reported to be expressed at high levels in embryonic stem cells, and iPSCs and microRNAs have been shown to alter cell phenotypes.

The investigators performed a simple experiment and expressed the microRNAs in mouse fibroblasts and were surprised to observe colonies that looked just like iPSCs. "We were very surprised that this worked the very first time we did the experiment," says Morrisey. "We were also surprised that it worked much more efficiently than the transcription factor approach pioneered by Dr. Yamanaka."

Since microRNAs act as repressors of protein expression, it seems likely that they repress the repressors of the four transcription factors and other factors important for maintaining the pluripotent-stem-cell state. However, exactly how the miRNAs work differently compared to the transcription factors in creating iPSCs will require further investigation.

The iPSCs generated by the microRNA method in the Morrisey lab are able to generate most, if not all, tissues in the developing mouse, including germ cells, eggs and sperm. The group is currently working with several collaborators to redifferentiate these iPSCs into cardiomyocytes, hematopoietic cells, and liver hepatocytes.

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Penn Medicine News: A New Way to Make Reprogrammed Stem Cells

PHILADELPHIA Given the amount of angst over male pattern balding, surprisingly little is known about its cause at the cellular level. In a new study, published in the Journal of Clinical Investigation, a team led by George Cotsarelis, MD, chair of the Department of Dermatology at the University of Pennsylvania School of Medicine, has found that stem cells play an unexpected role in explaining what happens in bald scalp.

Using cell samples from men undergoing hair transplants, the team compared follicles from bald scalp and non-bald scalp, and found that bald areas had the same number of stem cells as normal scalp in the same person. However, they did find that another, more mature cell type called a progenitor cell was markedly depleted in the follicles of bald scalp.

The researchers surmised that balding may arise from a problem with stem-cell activation rather than the numbers of stem cells in follicles. In male pattern balding, hair follicles actually shrink; they dont disappear. The hairs are essentially microscopic on the bald part of the scalp compared to other spots.

We asked: Are stem cells depleted in bald scalp? says Cotsarelis. We were surprised to find the number of stem cells was the same in the bald part of the scalp compared with other places, but did find a difference in the abundance of a specific type of cell, thought to be a progenitor cell, he says. This implies that there is a problem in the activation of stem cells converting to progenitor cells in bald scalp.

At this point, the researchers dont know why there is a breakdown in this conversion. However, the fact that there are normal numbers of stem cells in bald scalp gives us hope for reactivating those stem cells, notes Cotsarelis.

In 2007, the Cotsarelis lab found that hair follicles in adult mice regenerate by re-awakening genes once active only in developing embryos. The team determined that wound healing in a mouse model created an embryonic window of opportunity to manipulate the number of new hair follicles that form. By activating dormant embryonic molecular pathways stem cells were coaxed into forming new hair follicles.

In the JCI study, the group also found a progenitor cell population in mice that is analogous to the human cells; these cells were able to make hair follicles and grow hair when injected into an immunodeficient mice.

The researchers say their next steps will be to study the stem and progenitor populations in other types of hair loss, including female pattern hair loss. The information may assist in developing cell-based treatments for male pattern baldingby isolating stem cells and expanding them to add back to the scalp directly.They will also focus on identifying factors that could be used topically to convert stem cells to progenitor cells to generate normal large hairs.

First author Luis Garza, MD, PhD, a dermatologist and former postdoctoral fellow in the Cotsarelis lab, performed much of the work and is now an assistant professor of Dermatology at Johns Hopkins University.

The research was funded in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the Pennsylvania Department of Health; theFannie Gray Hall Center for Human Appearance; and LOreal.

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Penn Medicine News: Male Pattern Balding May Be Due to ...