Stem Cell Clinic

Discovery of epigenetic links in cell-fate decisions of adult stem cells paves way for new osteoporosis treatments

ScienceDaily (July 9, 2012) The ability to control whether certain stem cells ultimately become bone cells holds great promise for regenerative medicine and potential therapies aimed at treating metabolic bone diseases.

Now, UCLA School of Dentistry professor and leading cancer scientist Dr. Cun-Yu Wang and his research team have made a significant breakthrough in that direction. The scientists have discovered two key epigenetic regulating genes that govern the cell-fate determination of human bone marrow stem cells.

Wang's new research is featured on the cover of the July 6 issue of Cell Stem Cell, the affiliated journal of the International Society for Stem Cell Research.

The groundbreaking study grew out of Wang's desire to better understand the epigenetic regulation of stem cell differentiation, in which the structure of genes is modified while the sequence of the DNA is not. He and his team found that KDM4B and KDM6B, two gene-activating enzymes, can promote stem cells' differentiation into bone cells by removing methyl markers from histone proteins. This process occurs through the activation of certain genes favoring a commitment to one lineage and the concurrent deactivation of genes favoring other lineages.

The findings imply that chemical manipulation of these gene-activating enzymes may allow stem cells to differentiate specifically into bone cells, while inhibiting their differentiation into fat cells. The group's research could pave the way toward identifying potential therapeutic targets for stem cell-mediated regenerative medicine, as well as the treatment of bone disorders like osteoporosis, the most common type of metabolic bone disease.

"Through our recent discoveries on the lineage decisions of human bone marrow stem cells, we may be more effective in utilizing these stem cells for regenerative medicine for bone diseases such as osteoporosis, as well as for bone reconstruction," Wang said. "However, while we know certain genes must be turned on in order for the cells to become bone-forming cells, as opposed to fat cells, we have only a few clues as to how those genes are switched on."

The research group, through its study of aging mice, found that the two enzymes KDM4B and KDM6B could specifically activate genes that promote stem cell differentiation toward bone, while blocking the route toward fat.

"Interestingly, in our aged mice, as well as osteoporotic mice, we observed a higher amount of silencing histone methyl groups which were normally removed by the enzymes KDM4B and KDM6B in young and healthier mice," Wang said. "And since these enzymes can be easily modified chemically, they may become potential therapeutic targets in tissue regeneration and treatment for osteoporosis."

"The discovery that Dr. Wang and his team have made has considerable implications for craniofacial bone regeneration and treatment for osteoporosis," said Dr. No-Hee Park, dean of the UCLA School of Dentistry. "As a large portion of our population reaches an age where osteoporosis and gum disease could be major health problems, advancements in aging-related treatment are very valuable."

Professor Wang holds the No-Hee Park Endowed Chair in Dentistry at the UCLA School of Dentistry, where he is also chair of the division of oral biology and medicine and the associate dean for graduate studies.

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Discovery of epigenetic links in cell-fate decisions of adult stem cells paves way for new osteoporosis treatments

Antibodies from rabbits improve survival of leukemia and myelodysplasia patients receiving stem cell transplant

ScienceDaily (July 6, 2012) Researchers at Virginia Commonwealth University (VCU) Massey Cancer Center's Bone Marrow Transplant Program have demonstrated that the use of antibodies derived from rabbits can improve the survival and relapse outcomes of leukemia and myelodysplasia patients receiving a stem cell transplant from an unrelated donor.

Recently published in the journal Bone Marrow Transplantation, a study led by Amir Toor, M.D., hematologist-oncologist in the Bone Marrow Transplant Program and member of the Developmental Therapeutics program at VCU Massey Cancer Center, retrospectively compared the outcomes of 50 patients who received rabbit anti-thymocyte globulin (ATG) before receiving a transplant of stem cells from an unrelated donor to the outcomes of 48 patients who received a transplant of stem cells from a related donor. While unrelated stem cell transplants typically have poorer outcomes than related stem cell transplants, the results from this study showed similar outcomes for each group in terms of mortality, relapse and the development of graft-versus-host disease (GVHD), a common complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body.

"Unfortunately, we can't always find a related (genetically similar) donor for patients in need of stem cell transplantation," says Toor, who is also associate professor of internal medicine in the Department of Hematology, Oncology and Palliative Care at VCU School of Medicine. "Obtaining better outcomes with unrelated donor stem cell transplants could represent a significant advancement in extending the lives of more patients with blood cancers."

Unrelated donor stem cell transplants are generally considered a high-risk treatment due to historically higher rates of disease relapse and GVHD in comparison to stem cells transplanted from donors related to the patients. The results of the study indicated no survival differences between the two groups of patients regardless of age or diagnosis. Relapse rates and incidence of GVHD were also similar. Chronic GVHD, on the other hand, was diagnosed less frequently in patients in the ATG group. In addition, the researchers noticed a higher rate of infections in patients receiving the highest dose of ATG, but this risk was diminished in patients who received slightly lower doses.

This study is one of the first to use ATG in stem cell transplantation. ATG works by reducing the number of circulating T-lymphocytes, a key component of the immune system. It is primarily used in organ transplantation to prevent patients' immune systems from rejecting transplanted tissue. It is also used to treat aplastic anemia, a condition where the bone marrow does not create enough new cells. Currently, there are two types of ATG agents available for clinical use. The one used in this study is derived from rabbit antibodies while the other is derived from horse antibodies.

"Our study results should serve as a guide for designing future clinical trials using ATG to improve outcomes in unrelated donor stem cell transplants," says Toor. "Our findings are encouraging. If many of the risks commonly associated with unrelated donor stem cell transplants are reduced, transplantation becomes an option for more patients."

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The above story is reprinted from materials provided by Virginia Commonwealth University, via EurekAlert!, a service of AAAS.

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Antibodies from rabbits improve survival of leukemia and myelodysplasia patients receiving stem cell transplant

Annabelle magpapa-stem cell na rin

Nakatanggap ako kahapon ng phone call mula kay Annabelle Rama dahil type na rin niya na sumailalim sa stem cell treatment sa Germany.

Sa totoo lang, happy ako dahil na-discover sa Germany ang stem cell treatmentdahil talagang worth it na dayuhin, kesehodang isang araw ang tagal ng biyahe mula sa Pilipinas.

Plano ni Bisaya na gawin ang stem cell treatment sa third week ng July at in-encourage ko siya na ituloy ang kanyang balak dahil maganda talaga ang epekto sa katawan.

Rubby waging 2012 CEO excel

Congrats sa aking friend na si Rubby Sy ng Flawless dahil isa siya sa mga awardee ng 2012 CEO Excel (Communication Excellence in Organizations) na pinili ng Board of Trustees ng International Association of Business Communicators (IABC).

Hindi nakakagulat na napili si Rubby na awardee dahil siya ang sikreto kaya very successful ang Flawless, ang leading facial clinic ng bansa.

Doble ang tagumpay ni Mama Rubby dahil kabilang siya sa mga tumanggap ng Go Negosyo Outstanding Entrepreneur citation. Pararangalan si Mama Rubby ng CEO EXCEL sa awarding ceremonies na gaganapin sa July 12 sa Intercontinental Hotel, Makati City.

Tuwang-tuwa siya siyempre sa parangal na matatanggap niya.

Very thankful siya dahil ang pakiramdam niya, blessed na blessed siya.

We are just really working hard at Flawless every day. This award is a bonus.I couldnt have done it without my equally hardworking team. This award is really for all of us, ang nagpapasalamat na statement ni Mama Rubby.

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Annabelle magpapa-stem cell na rin

Diabetes drug helps brain growth, makes mice smarter

SACRAMENTO, CA. - A drug used to treat diabetes encourages the brain to grow and repair itself, afinding with far-reaching implications for the treatment of Alzheimers and brain injury, a new study published in Cell: Stem Cell reports.

The widely used diabetes drug metformin comes with the unexpected side effect of causing the growth of new neurons in the brain and makes mice smarter, the July 6th issue of Cell Stem Cell, a Cell Press publication, said. The study has potentially wide-reaching implications for the treatment of Alzheimers in humans and brain related injury.

The discovery has important implications for brain repair because it works not by introducing new stem cells but rather by spurring those that are already present into action, said the study's lead author Freda Miller of the University of Toronto-affiliated Hospital for Sick Children. And since the drug is already so widely used and so safe it means doctors could quickly begin using the drug for brain therapy treatment.

Earlier work by Miller's team highlighted a pathway known as aPKC-CBP for its essential role in telling neural stem cells where and when to differentiate into mature neurons, the report said. Other researchers had found before them that the same pathway is important for the metabolic effects of the drug metformin, but in liver cells.

"We put two and two together," Miller says. If metformin activates the CBP pathway in the liver, they thought, maybe it could also do that in neural stem cells of the brain to encourage brain repairm, he said.

Mice taking metformin not only showed an increase in the birth of new neurons, but they proved to become smarter by being better able to learn the location of a hidden platform in a standard maze test of spatial learning. The new evidence lends support to that promising idea in both mouse brains and human cells.

While it remains to be seen whether the very popular diabetes drug might already be serving as a brain booster for those who are now taking it, there are early hints the drug may have cognitive benefits for people with Alzheimer's disease. Scientists had speculated those improvements were the result of better diabetes control, Miller says, but it now appears that metformin may improve Alzheimer's symptoms by enhancing brain repair.

Miller says they now hope to test whether metformin might help repair the brains of those who have suffered brain injury due to trauma or radiation therapies for cancer.

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Diabetes drug helps brain growth, makes mice smarter

New FDA-approved stem cell study gives hope to family

LABELLE, Fla.- Two-year old Madeline Conner was born with the inability to hear. But new advances in medical science could offer hope in the form of a stem cell research study.

"I really wanted her in it. It was our one shot," said her mother, Stephanie Conner.

Conner heard about a new FDA-approved stem cell study for hearing loss. She knew right away her little girl was the perfect candidate.

"It's a group of ten kids and she's the first one and the only one so far," she said.

The trial is a collaboration between Children's Memorial Hermann Hospital in Houston and the California-based Cord Blood Registry. "This is the first study FDA regulated looking at the safety and benefit of cord blood stem cells for treatment of acquired sensorineural hearing loss. Which is loss that has to do with the damage of the inner ear and nerve fibers that go to the brain," said Principal Investigator, Dr. Fakhri.

Stem cells, saved from Madeline's own umbilical cord, were injected into her arm.

"We expect that it will be safe. You are using your own blood stem cells as if it was your own transfusion," stated Dr. Fakhri. "It was actually a one-time treatment, just one infusion. Then we keep going, We go four times total, just so they can check her and compare all the testing they did before hand to see if there has been any improvement," said her mom.

In theory, the treatment will adjust Madeline's immune system and will help her body repair itself. In reality, researchers say they have no idea if it will work.

"We've definitely seen a lot of improvement. It's hard to say if it's 100 percent because of this or that. It's just our observation," said Madeline's parents.

"We can not expect what the results will be, but potentially it can repair and restore normal hearing," Fakhri said.

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New FDA-approved stem cell study gives hope to family

Critical process in stem cell development identified

ScienceDaily (July 5, 2012) Scientists at the Gladstone Institutes have discovered that environmental factors critically influence the growth of a type of stem cell -- called an iPS cell -- that is derived from adult skin cells. This discovery offers newfound understanding of how these cells form, while also advancing science closer to stem cell-based therapies to combat disease.

Researchers in the laboratory of Gladstone Senior Investigator Shinya Yamanaka, MD, PhD, have for the first time shown that protein factors released by other cells affect the "reprogramming" of adult cells into stem cells known as induced pluripotent stem cells, or iPS cells. The scientists -- who collaborated on this research with colleagues from the University of California, San Francisco (UCSF) -- announce their findings July 5 online in Cell Stem Cell.

In 2007, Dr. Yamanaka discovered a recipe of specific proteins to add to human skin cells as a way to induce them into becoming iPS cells -- which act very much like embryonic stem cells. Many see iPS cell technology as a new platform for drug discovery and the study of disease fundamentals -- while avoiding the ethical issues surrounding research involving embryonic stem cells. But questions remain about the most efficient way to cultivate iPS cells.

"We've reinforced our hypothesis that the cell's environment is vital to the reprogramming process," said Dr. Yamanaka, who did his postdoctoral studies at Gladstone in the 1990s, returning here in 2007 as a senior investigator. "We can now expand our understanding of cell development -- and use iPS cells to model conditions such as Alzheimer's and heart disease."

Normally when researchers convert skin cells into iPS cells, the cells rest on a special layer of materials in a petri dish. The layer includes "feeder" cells that provide nutrients required for the iPS cells to grow and reproduce. In this study, performed at the Roddenberry Center for Stem Cell Biology & Medicine at Gladstone, scientists generated human iPS cell lines by using a method in which the feeder layer secretes a protein called LIF. Dr. Yamanaka, who invented this so-called "Kyoto" method, also directs the Center for iPS Cell Research and Application at Kyoto University and is a professor at UCSF, with which Gladstone is affiliated. UCSF collaborators on this research include co-senior author Barbara Panning, PhD, and Karen Leung, PhD.

The researchers then analyzed LIF's importance in the growth of female iPS cells. Female iPS cells contain two copies of the X-chromosome, which is one of two sex chromosomes. While males carry one X and one Y-chromosome, females' two X-chromosomes could result in a potentially toxic double dose of genes -- except for a unique evolutionary mechanism whereby one of the two X's is silenced in a process known as "X-inactivation." This process, which occurs early during the development of the embryo, ensures that females, like males, have one functional copy of the X-chromosome in each cell. But exactly how X-inactivation happens is unknown.

To research this, Gladstone scientists generated female iPS cells on feeder layers without LIF and found that one of the X-chromosomes in each iPS cell remained silent. Those iPS cells that grew on a layer of cells with the LIF protein, however, grew with two activated X-chromosomes. Then, by taking a cell from a non-LIF cell layer and transferring it to a LIF-cell layer, the iPS cell's inactive X-chromosome switched on and became even more like embryonic stem cells. These results are crucial for future studies of how iPS cells grow and mature. And because this iPS technology lets scientists create stem cells from patients with a specific disease, this new finding could lead to a far-superior human model for studying disease and testing new drugs.

"These results will make it possible to readily generate stable, double-active, higher-quality X-chromosome iPS cells, and study the process more closely," said Gladstone Research Scientist Kiichiro Tomoda, PhD, who is the paper's lead author "Our findings also reinforce work from other Gladstone scientists showing that the cell environment is critical to the reprogramming process."

Other scientists who participated in this research at Gladstone include Kirsten Eilertson, PhD, Mark White, Salma Sami, Bruce Conklin, MD and Deepak Srivastava, MD. Funding came from a variety of sources, including the California Institute for Regenerative Medicine, the National Institutes of Health, the Roddenberry Foundation and the L.K. Whittier Foundation.

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Critical process in stem cell development identified

Mrs. Itana, a diabetic nephropathy from Papua New Guinean for Stem Cells and TCM Treatment – Video

02-07-2012 21:07 Mrs Itana was diagnosed with diabetic nephropathy 15 years ago and in February, 2012 she was told by her doctor her kidneys did not work well and dialysis was necessary. Before she came to China for STEM CELL and TRANDITIONAL CHINESE MEDICINE TREATMENT, she was hospitalized in local couple of times because she was very weak and had short of breath, heart failure and so many. After the first stem cells transplant, she felt she was back 16 years old person and so energetic. Therefore, she wants to share his treatment experiences to all kidney disease patients and wish her words and successful experience can be widely spread out. And, more of the cancer patients can seek for the proper treatment in China. And yet, in her country Mrs Itana only has one choice -- kidney transplant.

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Mrs. Itana, a diabetic nephropathy from Papua New Guinean for Stem Cells and TCM Treatment - Video