UF Scientists Program Blood Stem Cells To Become Vision Cells - Uncategorized

University of Florida researchers were able to program bone marrow stem cells to repair damaged retinas in mice, suggesting a potential treatment for one of the most common causes of vision loss in older people.

The success in repairing a damaged layer of retinal cells in mice implies that blood stem cells taken from bone marrow can be programmed to restore a variety of cells and tissues, including ones involved in cardiovascular disorders such as atherosclerosis and coronary artery disease.

“To our knowledge, this is the first report using targeted gene manipulation to specifically program an adult stem cell to become a new cell type,” said Maria B. Grant, M.D., a professor of pharmacology and therapeutics at UF’s College of Medicine. “Although we used genes, we also suggest you can do the same thing with drugs – but ultimately you would not give the drugs to the patient, you would give the drugs to their cells. Take the cells out, activate certain chemical pathways, and put the cells back into the patient.”

In a paper slated to appear in the September issue of the journal Molecular Therapy, scientists describe how they used a virus carrying a gene that gently pushed cultured adult stem cells from mice toward a fate as retinal cells. Only after the stem cells were reintroduced into the mice did they completely transform into the desired type of vision cells, apparently taking environmental cues from the damaged retinas.

After studying the cell-transformation process, scientists were able to bypass the gene manipulation step entirely and instead use chemical compounds that mirrored environmental conditions in the body, thus pointing the stem cells toward their ultimate identities as vision cells.

“First we were able to show you can overexpress a protein unique to a retinal cell type and trick the stem cell into thinking it is that kind of cell,” said Grant, who collaborated with Edward Scott, Ph.D., the director of the Program in Stem Cell Biology and Regenerative Medicine at UF’s McKnight Brain Institute. “As we proceeded, we found we could activate the stem cells by mimicking the body’s natural signaling channels with chemicals. This implies a whole new field of stem cell research that uses drug manipulation rather than genetic manipulation to send these immature cells along new pathways.”

Scientists chose to build retinal pigment epithelial cells, which form the outer barrier of the retina. In addition to being very specialized and easy to identify, RPE cells are faulty in many retinal diseases, including age-related macular degeneration, which affects nearly 2 million people in the United States, and some forms of blindness related to diabetes.

“This work applies to 85 percent of patients who have age-related macular degeneration,” Grant said. “There are no therapies for this devastating disease.”

The work was supported by the National Eye Institute. Researchers removed blood stem cells from the bone marrow of mice, modified the cells in cultures, and injected them back into the animals’ circulatory systems. From there, the stem cells were able to home in on the eye injury and become retinal cells.

At 28 days after receiving the modified stem cells, mice that had previously demonstrated no retinal function were no different than normal mice in electrical measures of their response to light.

Grant and UF have patented some technology involved in the research.

Source
University of Florida Health Science Center

UF Scientists Program Blood Stem Cells To Become Vision Cells

Originally from:
http://www.medicalnewstoday.com/articles/159466.php

I want to donate cord blood but not for myself and i didnt know if it was free. Has anybody done this through a reliable company that i can trust giving my personal information? Thank you.

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Journal retracts UK study claiming to have created human sperm from stem cells

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A research team comprised of faculty at Worcester Polytechnic Institute’s (WPI) Life Sciences and Bioengineering Center (LSBC) and investigators at CellThera, a private company also located at the LSBC, has discovered a novel way to turn on stem cell genes in human fibroblasts (skin cells) without the risks associated with inserting extra genes or using viruses. This discovery opens a new avenue for reprogramming cells that could eventually lead to treatments for a range of human diseases and traumatic injuries by coaxing a patient’s own cells to repair and regenerate the damaged tissues.

The research team reported its findings in the paper “Induction of Stem Cell Gene Expression in Adult Human Fibroblasts without Transgenes,” published online July 21, 2009 (in advance of September print publication) as a “fast track” paper from the journal Cloning and Stem Cells. (Cloning, Stem Cells. 2009 Jul 21.) “We show that by manipulating culture conditions alone, we can achieve changes in fibroblasts that would be beneficial in development of patient-specific cell therapy approaches,” the authors wrote in the paper.

Early on, the emerging field of regenerative medicine focused on embryonic stem cells, which are pluripotent, meaning they can grow into all the tissues of an adult organism. In the pluripotent state, several genes are known to be active, helping to control the stem cells. These genes, including OCT4, SOX2 and NANOG, are accepted as markers of pluripotency because they are active in stem cells, but become dormant once the stem cells begin to differentiate and head down the path to developing into a specific kind of cell type and tissue.

While the study of embryonic stem cells continues to yield important knowledge, research teams around the world are also working to change, or reprogram, fully-differentiated cells like skin cells, back to a more pluripotent state. Called induced pluripotent stem cells (iPS), these reprogrammed cells could be used to regenerate tissue without some of the problems associated with embryonic stem cells, including ethical questions and the potential for embryonic stem cells to be rejected by a patient’s immune system or to grow out of control and cause tumors.

The first induced pluripotent stem cells were created in 2007 by Shinya Yamanaka’s team at Kyoto University in Japan, which inserted extra copies of four known stem cell genes, including OCT4 and SOX2, into human skin cells. Those genes began expressing proteins that changed the skin cells back to a more pluripotent state. This technique, which has since been repeated by other labs and refined to the point were fewer additional genes are needed to achieve reprogramming, was a major scientific breakthrough. Its potential for use in human therapies is limited, however, because inserting new genes into adult cells, either directly or by using viruses to carry the genetic payload, can cause a host of problems.

In the current study, the team at WPI and CellThera turned on the existing, yet dormant, stem cell genes OCT4, SOX2 and NANOG already in the skin cells by lowering the amount of atmospheric oxygen the cells were exposed to, and by adding a protein called fibroblast growth factor 2 (FGF2) to the culture medium. (FGF2 is a naturally occurring protein that is known to be vital for maintaining the pluripotency of embryonic stem cells.)

Furthermore, once the stem cell genes were activated and began expressing proteins, the team found those proteins migrated back into the nucleus of the skin cells, precisely as would occur in induced pluripotent stem cells. “This was an exciting observation,” said Raymond Page, PhD, research assistant professor of biology and biotechnology at WPI and lead author on the paper. “Having these proteins localize to the nucleus is the first step of reprogramming these cells.”

Even more surprising, the team found that the stem cell genes OCT4, SOX2 and NANOG were not completely dormant in untreated skins cells, as was presumed. Those genes were, in fact, sending out messages, but those messages were not being translated into the proteins that do the work of making cells pluripotent. “This was quite unexpected,” said Tanja Dominko, DVM, PhD, associate professor of biology and biotechnology at WPI and president of CellThera. “Not only does this data force us to rethink what the true markers of pluripotency may be, it suggests there is a natural mechanism at work in these cells regulating the stem cell gene expression. That opens a whole new line of inquiry.”

The work in the current study was supported by WPI startup funds and a grant to Dr. Dominko from the National Institutes of Health, and by funding to CellThera from the U.S. Defense Advanced Research Projects Agency (DARPA) and the Army Research Office (ARO).

Source:
Michael Cohen

Worcester Polytechnic Institute

Reprogramming Human Cells Without Inserting Genes

Originally from:
http://www.medicalnewstoday.com/articles/159361.php

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NY women could soon get up to $10K to donate eggs for stem cell study _ paid for by taxpayers

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Stem cell research promises remedies to many devastating diseases that are currently incurable, ranging from diabetes and Parkinson’s disease to paralysis. Totipotent embryonic stem cells have great potential for generating a wide range of different human cells that can be used to restore malfunctioning or damaged cells and tissues in patients. Recent studies have shown that pluripotent stem cells derived from adult bone marrow, the umbilical cord and the placenta could also be induced to differentiate into a variety of different tissues. In this issue, we have invited several scientists in China to summarize their pioneering works in the stem cell research field.

Since 2001, Dr. Alex Yu Zhang has been a professor at Capital Medical University in Beijing and is Director of Cell Therapy Center at Xuanwu Hospital. His current research interest focuses on the understanding of basic biological properties of stem cells and developing nonhuman primate models for stem cell-based therapy of degenerative diseases. He has developed a stem cell mediated expression system for treating Parkinson’s disease and his research using pancreatic progenitor cells for treating diabetes has demonstrated efficacy in monkey models. Professor Zhang has written an overview of cell replacement therapy of Parkinson’s disease, which has been studied in both animal models and human patients for more than 20 years. Recent progress in stem cell biology has indicated that it is possible to avoid immunorejection of either nuclear transfer embryonic stem cells or induced pluripotent stem cells. On the other hand, recent post mortem analysis of patients who received fetal brain cell transplantation revealed that implanted cells are prone to degeneration just like endogenous neurons. Thus it appears that future cell replacement studies will have to focus on ameliorating disease symptoms as well as on slowing the progression of the disease[1].

Professor Robert Chunhua Zhao from the Chinese Academy of Medical Sciences is Executive Director of the National Center for Stem Cell Research. His group has taken stem cell therapy into phase II clinical trials in China, and is the leading runner in stem cell therapeutics. They have identified a mesenchymal stem cell (MSC) population from human fetal bone marrow and found that these cells could differentiate not only into osteogenic, adipogenic and endothelial lineages, but also hepatocyte-like cells, and neural and erythroid cells. They remained in some tissues and organs during gestation and could give rise to different kinds of pluripotent stem cells and thus could potentially contribute to self-repair and self-renewal of tissues and organs. They generated cells not only for the damaged tissues in which they reside, but also for damaged tissues at other locations in the body via migration triggered by proinflammatory cytokines and growth factors. The potential use of MSCs in tissue regeneration has been shown in several models, including skin, muscle, lung, heart and the small intestine. MSCs have emerged as a promising therapeutic modality for tissue regeneration and autoimmune disease, although the mechanisms underlying the immune-modulatory effects of MSCs have not yet been clearly defined. In this review, Professor Robert Zhao summarizes the current literature on the complex mechanism of MSCs’ immune modulation and clinical studies, and discusses future directions for utilizing MSCs for clinical treatments[2].

Professor Hongkui Deng from Peking University is working on the differentiation of human embryonic stem cells into pancreatic beta cells to treat diabetes. He is one of the two winners in China of the Bill and Melinda Gates Foundation’s “Grand Challenges in Global Health”. He obtained $1.9 million for his proposal to use stem cells to create mouse models for testing HIV and hepatitis C vaccines. Professor Deng has written a summary of recent progress in human embryonic and inducible pluripotent stem cell differentiation into functional pancreatic islet cells and discusses the challenges for future work[3].

Professor Qi Zhou is assistant Director of the Institute of Zoology at the Chinese Academy of Sciences. He has been studying the mechanism of differentiation and de-differentiation, cellular plasticity and totipotency of pluripotent cells, as well as that of somatic cells. He intends to build various cellular and animal models for human diseases, to uncover mechanisms underlying these different cellular processes and to discover new ways to improve cloning efficiency, which will provide a powerful tool for the study of mammalian reprogramming and ultimately offer important opportunities for regenerative medicine. Professor Zhou has helped to build the National Stem Cell Bank in Beijing, where clinical grade stem cell lines and patient specific cell lines have been created for future drug target candidate screening and therapeutic applications. Professor Qi Zhou has written a summary on human parthenogenetic embryonic stem cells as one potential resource for stem cell therapy[4].

Professor Lin Liu from Nankai University has been working on creating versatile patient-specific pluripotent stem cell lines that can be reliably used to fulfill the promise of stem cell therapy in regenerative medicine. Dr. Lin Liu’s group found that pES cells generated from immature oocytes in mice exhibit pluripotency resembling fES cells, as evidenced by similarly high chimera production and germline transmission. Thus, immature eggs may provide an efficient source of autologous stem cells for regenerative medicine. This group also tested whether pESCs can be generated from older females. Drs. Lingyi Chen works on mechanisms of early embryonic differentiation. In their review of current special topics on stem cells, Drs. Lingyi Chen and Lin Liu analyze the current state of iPS research, particularly on limitations and advancements in this field, and propose possible future directions to meet the challenges of iPS cells for clinical applications[5].

Stem cell research has made significant progress in the past decade. Some therapeutic applications are coming closer to being on the market, but it is still hard to predict if and when stem cell therapy will replace largely traditional therapeutics. Given the early indications for success, we hope to see promising remedies for the many current uncurable diseases being made available in the clinic over the coming years.

Notes:

1. Ren Z, Zhang Y. Cell therapy for Parkinson’s disease – So close and so far away. Sci China C-Life Sci, 2009, 52: 610-614

2. Wang L, Zhao R C. Mesenchymal stem cells targeting the GVHD. Sci China C-Life Sci, 2009, 52: 603-609
3. Zhang D, Jiang W, Shi Y, et al. Generation of Pancreatic islet cell from human embryonic stem cell. Sci China C-Life Sci, 2009, 52: 615-621
4. Hao J, Zhu W, Sheng C, et al. Human parthenogenetic embryonic stem cells: One potential resource for cell therapy. Sci China C-Life Sci, 2009, 52: 622-636
5. Chen L, Liu L. Current progress and prospect of induced pluripotent stem cell. Sci China C-Life Sci, 2009, 52: 622-636

Source:
Li Jiyuan

Science in China Press

From Molecular Physiology To Therapeutic Applications Of Stem Cells

Originally from:
http://www.medicalnewstoday.com/articles/159333.php

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In what will be the Stem Cell Awareness Association’s seventh awareness rally, past patients, interested physicians, and prospective patients will meet in Manchester to learn about stem cell technologies and discuss the various current treatments available throughout the world.

Stem cell advocate Darren Clarke is organizing the Manchester event. Mr. Clarke became involved in stem cell advocacy early in his daughter, Dakota’s, life. At three years old, Dakota became the first child from Britain and Ireland to be treated for septo-optic dysplasia (SOD) in China. She was born blind but began to regain her vision just weeks into her stem cell treatment. Her parents have been passionate stem cell advocates ever since.

Darren said, “I felt that western medical opinion directed people away from the treatments available to people with problems like Dakota’s. It’s my aim to let people see that there is an option out there. If I can spread the news that it works and that there is hope, then all the effort will be worthwhile.”

To read more about Dakota Clarke, details can be found on Dakota’s website.

Peter Conry, a Dublin pharmacist and pharmaceutical industry veteran interested in stem cell technology, will be speaking at the event about how his work and travel throughout Asia transformed him from being a medically trained skeptic to informed stem cell advocate. Peter states, “I visited stem cell treatment facilities and spoke at length with patients and staff. I came away convinced I’d witnessed the start of a significant medical advance.”

Shel Morse, stem cell advocate and mother of Macie Morse, will be attending from Colorado to share the story of her daughter, Macie, who regained vision after stem cell treatment in China. Macie, at 15 years old, was denied a driver’s permit because optic nerve hypoplasia (ONH) had left her legally blind. After stem cell treatment in China, Macie returned to the States and one year later had the required vision to pass the test.

Mrs. Morse said, “Because of what stem cells have done for my daughter, I am now on a mission to help bring awareness to as many people as possible. It’s time to empower the people to make informed choices based on what is really available out there.”

Also in attendance will be Luca Ricci from Shenzhen Beike Biotechnology, which provided the stem cells for Macie Morse’s treatment. Mr. Ricci will be speaking about current treatments offered and answering patient questions about the therapy process — from initially contacting Beike to life in China to returning home.

This U.K. rally will be the association’s first event held outside of the United States and will follow in the footsteps of previous events by creating a community where stem cell patients have the opportunity to share their experiences with prospective patients. It will also provide an opportunity for doctors and medical specialists to not only connect with patients but also consider how stem cell technology can be successfully applied not just overseas, but locally.

All patients who are interested, who are considering stem cell treatments or who have already had stem cell treatments are welcome to join the U.K. Stem Cell Awareness Rally:

Location: Manchester, England
Place: The Thistle Manchester Hotel
Date: August 9th, 2009
Time: 10 a.m.

More information about the event can be found at the Stem Cell Awareness Association’s web site.

Source
Stem Cell Awareness Association

First U.K. Stem Cell Awareness Rally To Take Place In Manchester, England On August 9th, 2009

Originally from:
http://www.medicalnewstoday.com/articles/159327.php

New way to reprogram skin cells without inserting genes discovered

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Researchers have found a way to directly convert spermatogonial stem cells, the precursors of sperm cells, into tissues of the prostate, skin and uterus. Their approach, described this month in the journal Stem Cells, may prove to be an effective alternative to the medical use of embryonic stem cells.

The hunt for alternatives to embryonic stem cells has led to some promising yet problematic approaches, some of which involve spermatagonial stem cells (SSCs). Researchers recently observed, for example, that SSCs grown in the laboratory will eventually give rise to a few cells that look and act like embryonic stem cells. This process can take months, however, and only a small percentage of the SSCs are converted into “embryonic stem-like” cells.

Other researchers have used viruses to insert genes into SSCs that will spur them to turn into ES-like cells. But this approach is problematic and the use of viruses to ferry in the needed genes has caused concern.

The new method, recently developed at the University of Illinois, takes advantage of the unusual interaction of two tissue types: the epithelium and the mesenchyme. The epithelium lines the cavities and surfaces of glands and many organs and secretes enzymes and other factors that are essential to the function of these tissues. The mesenchyme is the connective tissue in embryos. (In adults, the connective tissue is called stroma.)

In the 1950s, scientists discovered that the epithelium takes its developmental instructions from the mesenchyme. For example, when researchers put bladder epithelial cells on the mesenchyme of a prostate gland, the bladder cells were changed into prostatic epithelium. The prostatic mesenchyme had altered the fate of the bladder epithelium.

“The mesenchyme – it’s the director; it’s controlling the show,” said University of Illinois veterinary biosciences professor Paul Cooke, who led the new study with postdoctoral researcher Liz Simon.

Cooke began the effort with what even he considered an unlikely proposition.

“Could we take spermatagonial stem cells and cause them to directly change into other cell types by putting them with various mesenchymes and growing them in the body?” he said. “I thought it was possible, but I didn’t think it would work.”

The experiment did work, however. When Simon placed SSCs from inbred mice on prostate mesenchyme and grafted the combination into living mice, the SSCs became prostatic epithelium. When combined with skin mesenchyme and grown in vivo, the SSCs became skin epithelum. The researchers were even able to convert SSCs into uterine epithelium by using uterine mesenchyme.

The newly formed tissues had all the physical characteristics of prostate, skin or uterus, and produced the telltale markers of those tissue types, Cooke said. They also stopped looking and behaving like SSCs.

To assure that their tests were not contaminated with epithelial cells from the source of the mesenchyme cells, the researchers repeated the experiments using a mouse whose cells contained a gene that fluoresces green under ultraviolet light. The SSCs were obtained from a green-fluorescing mouse, but the mesenchyme came from a non-fluorescing mouse. This enabled the researchers to trace the fate of the SSCs. If the newly formed prostatic epithelium glowed green even though the mesenchyme did not, for example, the researchers knew that the SSCs had been converted into prostatic epithelium.

Cooke hopes that a more streamlined approach can be developed that makes use of a man’s own SSCs and stroma (the adult equivalent of the mesenchyme) to produce new skin cells or other tissues when needed – for example, to replace skin damaged in a burn. And his team is investigating the use of ovarian stem cells instead of SSCs to see if the same results can be obtained with ovarian tissue.

This work was supported by the Billie A. Field Endowment, the U. of I., and the National Institutes of Health.

“Direct Transdifferentiation of Stem/Progenitor Spermatogonia Into Reproductive and Nonreproductive Tissues of All Germ Layers” appears in Volume 27, Number 7, of the journal Stem Cells. The authors: Liz Simon, Gail C. Ekman, Natalia Kostereva, Zhen Zhang, Rex A. Hess, Marie-Claude Hofmann, Paul S. Cooke.

Source:
Diana Yates

University of Illinois at Urbana-Champaign

Male Germ Cells Can Be Directly Converted Into Other Cell Types

Originally from:
http://www.medicalnewstoday.com/articles/159188.php

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