July 2, 2014

News Review From Harvard Medical School -- Transplant May Help Adults with Sickle Cell

A partial transplant of bone-marrow stem cells may reverse sickle cell disease in adults, a new study finds. People with sickle cell disease have abnormally shaped red blood cells. They get stuck in blood vessels. This causes organ damage, pain and other medical problems. The new study included 30 adults with severe sickle cell disease. Each of them had a brother or sister who was a suitable match for a bone-marrow stem cell transplant. The sibling donor's cells were mixed with some of the patient's own cells. During 3.4 years of follow-up, the partial transplant reversed sickle cell disease in 26 out of 30 people, researchers said. In these patients, the bone marrow began making normal red blood cells. Fifteen people also were able to stop taking drugs to prevent rejection of the transplant. Overall, people were much less likely than before to need hospital treatment for the disease. Use of narcotic drugs for pain also was greatly reduced. The Journal of the American Medical Association published the study. HealthDay News wrote about it July 1.

By Howard LeWine, M.D.Harvard Medical School

What Is the Doctor's Reaction?

In the United States, more than 90,000 people are affected by sickle cell disease. Most of them are African-American. Worldwide, the number is much higher. About 300,000 babies are born with this genetic disease every year.

In sickle cell disease, the red blood cells made in the bone marrow are abnormal. Instead of having a normal round shape, the cells are curved and stiff. This causes the red blood cells to get stuck inside blood vessels before they reach the tissues. The result:

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News Review From Harvard Medical School -- Transplant May Help Adults with Sickle Cell

By Steven Reinberg HealthDay Reporter

TUESDAY, July 1, 2014 (HealthDay News) -- A new bone marrow transplant technique for adults with sickle cell disease may "cure" many patients. And it avoids the toxic effects associated with long-term use of anti-rejection drugs, a new study suggests.

This experimental technique mixes stem cells from a sibling with the patient's own cells. Of 30 patients treated this way, many stopped using anti-rejection drugs within a year, and avoided serious side effects of transplants -- rejection and graft-versus-host disease, in which donor cells attack the recipient cells, the researchers said.

"We can successfully reverse sickle cell disease with a partial bone marrow transplant in very sick adult patients without the need for long-term medications," said researcher Dr. John Tisdale, a senior investigator at the U.S. National Heart, Lung, and Blood Institute.

In the United States, more than 90,000 people have sickle cell disease, a painful genetic disorder found mainly among blacks. Worldwide, millions of people have the disease.

Many adults with sickle cell disease have organ damage. This makes them ineligible for traditional transplants, which destroy all their bone marrow cells and use unmatched donor cells, he said. "Doing it this way would allow them access to a potential cure," Tisdale said.

"Adult patients, in whom symptoms are very severe, should consider whether a transplant could be right for them," he said. "A simple blood test for their siblings could tell them whether this approach is an option."

One expert was enthusiastic about the report, published July 2 in the Journal of the American Medical Association.

"The outcomes look every bit as good, if not better, than anything reported so far," said Dr. John DiPersio, chief of the division of oncology at Washington University School of Medicine in St. Louis.

"The issue is whether this can be extended to unrelated donors and to mismatched donors," said DiPersio, also the author of an accompanying journal editorial.

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Less Toxic Transplant Treatment Offers Hope for Sickle Cell Patients

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Newswise INDIANAPOLIS -- Like a line of falling dominos, a cascade of molecular events in the bone marrow produces high levels of inflammation that disrupt normal blood formation and lead to potentially deadly disorders including leukemia, an Indiana University-led research team has reported.

The discovery, published by the journal Cell Stem Cell, points the way to potential new strategies to treat the blood disorders and further illuminates the relationship between inflammation and cancer, said lead investigator Nadia Carlesso, M.D., Ph.D., associate professor of pediatrics at the Indiana University School of Medicine.

Bone marrow includes the cells that produce the body's red and white blood system cells in a process called hematopoiesis. The marrow also provides a support system and "home" for the blood-producing cells called the hematopoietic microenvironment. The new research demonstrates the importance of the hematopoietic microenvironment in the development of a group of potentially deadly diseases called myeloproliferative disorders.

"It has been known for years that there are links between inflammation and cancer, but these studies have been challenged by the lack of genetic models, especially for blood-based malignancies," said Dr. Carlesso, a member of the hematologic malignancy and stem cell biology program within the Wells Center of Pediatric Research at IU.

The researchers focused on what happens when there are abnormally low levels of a molecule called Notch, which plays an important role in the process of blood cell production. Using a genetically modified mouse, they found that the loss of Notch function in the microenvironment causes a chain of molecular events that result in excess production of inflammatory factors.

The high levels of inflammation in the bone marrow were associated with the development of a myeloproliferative disorder in the mice. Myeloproliferative diseases in humans can result in several illnesses caused by overproduction of myeloid cells, which are normally are used to fight infections. These diseases can put patients at risk for heart attack or stroke, and frequently progress into acute leukemia and bone marrow failure, which have fatal outcomes. Unfortunately, there are no effective therapies for the majority of myeloproliferative diseases.

When Dr. Carlessos team blocked the activity of one of the molecules in this biochemical cascade, the myeloproliferative disorder in the mice was reversed. In addition, elevated levels of the blocked molecule were found in samples from human patients with myeloproliferative disease. These findings suggest that developing drugs that target this inflammatory reaction at different key points could be a promising strategy to limit the development of myeloproliferative disease in humans.

The molecular cascade leading to inflammation was not occurring directly in the bone marrow cells that produce blood cells, but in cells of the bone marrow microenvironment, especially in endothelial cells that line the capillaries -- tiny blood vessels -- inside the bone marrow. This was a key discovery, Dr. Carlesso said.

Continued here:
Biochemical Cascade Causes Bone Marrow Inflammation, Leading to Serious Blood Disorders

Last reviewed and revised on May 20, 2013

By Anthony L. Komaroff, M.D. Brigham and Women's Hospital

Both adult and umbilical cord stem cells already are used to treat disease.

Adult stem cells:

For many years, doctors have used adult stem cells successfully to treat human disease, through bone marrow transplantation (also known as hematopoietic stem cell transplantation). Most often, this treatment is used to treat cancers of the bloodlymphomas and leukemias. When all other treatments have failed, the only hope for a cure is to wipe out all of the patients blood cellsthe cancerous ones and the healthy onesand to give a patient an entirely new blood system. The only way to do this is to transplant blood stem cellscells that can reproduce themselves indefinitely and turn into all types of specialized blood cells.

Here's how it's done. First, the doctors need to collect blood stem cells from a patient's bone marrow, and let them multiply.

Second, the patient is given a dose of chemotherapy that kills all of the cancer cells a dose that, unfortunately, also kills the cells in the patient's bone marrow.

Third, the blood stem cellsthe cells designed to give the patient a whole new blood systemare given to the patient through an intravenous catheter. Hopefully, the blood stem cells then travel through the blood to the bone marrow, where they take up residence and start to make a new blood system.

Where do the blood stem cells come from? Most of the time, they come from the patient himself. They are sucked out of the patients bone marrow through a needle, or taken from the patients blood (some blood stem cells travel in the blood). So the blood stem cells are outside the patients body, growing in a laboratory dish, when the patient is given the chemotherapy that kills all the blood cells still inside the body.

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Special Harvard Commentary: How Stem Cells Help Treat Human Disease

hide captionThe heart beats in a mouse embryo grown with stem cells made from blood. Now the research that claimed a simple acid solution could be used to create those cells has been retracted.

The heart beats in a mouse embryo grown with stem cells made from blood. Now the research that claimed a simple acid solution could be used to create those cells has been retracted.

A prestigious scientific journal Wednesday took the unusual step of retracting some high-profile research that had generated international excitement about stem cell research.

The British scientific journal Nature retracted two papers published in January by scientists at the Riken research institute in Japan and at Harvard Medical School that claimed that they could create stem cells simply by dipping skin and blood cells into acid.

The claim raised the possibility of being able to use the cells to easily make any kind of cell in the body to treat many diseases and generated international media coverage, including some on Shots.

But other scientists almost immediately raised questions about the papers, and investigators eventually found that the research papers contained many errors. In April, Riken even concluded that Haruko Obokata, the main Japanese scientist, was guilty of scientific misconduct.

The scientists involved in the work, including Charles Vacanti at the Harvard-affiliated Brigham and Women's Hospital in Boston, issued statements regretting the problems with the papers and agreeing that they should be retracted.

"I am deeply saddened by all that has transpired, and after thoughtful consideration of the errors presented in the Riken report and other concerns that have been raised, I have agreed to retract the papers," Vacanti wrote in a statement.

But Vacanti and Obokata said they still believed their techniques could work. In fact, Riken recently agreed to allow Obokata to participate in an experiment aimed at attempting to reproduce the original results.

For its part, the journal Nature said it was reviewing its policies to try to prevent future flawed papers from being published and published retractions of the two original papers as well as the editorial that accompanied them.

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Easy Method For Making Stem Cells Was Too Good To Be True

When two scientific papers, published in the journal Nature in January, described an inexpensive, uncontroversial and quick method of creating stem cells, it was hailed as a path-breaking discovery.

However, five months later, the research stands discredited after Nature retracted the papers Wednesday, and the study's inclusion in the prestigious journal has cast doubts on its peer-review process. In a retraction published by Nature, the researchers admitted that several critical errors had been found in the article, and that these multiple errors impair the credibility of the study as a whole.

In the research papers published in January, scientists from the Riken Centre for Developmental Biology in Japan had described a process to convert mature skin cells into pluripotent stem cells. Pluripotent stem cells are embryonic -- like stem cells that can be grown into any kind cell, tissue or organ. The method described in the papers was fairly straightforward and involved immersing the cells in an acid bath to create what the researchers called Stimulus Triggered Acquired Pluripotency Stem Cells, or STAP-SC.

Currently, there are only two ways to create stem cells. One involves extracting stem cells from the embryo, which results in its destruction and is therefore considered controversial. The other method requires the insertion of DNA into adult cells and is extremely expensive. Furthermore, the stem cells created through the second method are unstable and mostly unviable due to the presence of foreign genetic material.

Since the method described in the papers did not require the destruction of an embryo or the insertion of foreign DNA, it was heralded as a revolutionary new breakthrough in stem-cell technology. However, soon after the publication of the papers, a number of errors came to light.

One of the scientists involved in the research, Teruhiko Wakayama, also called for a retraction in March. This led to an internal investigation by the Riken Centre, which found in April that the studys lead author, Haruko Obokata, had misrepresented data in her research papers.

In an editorial accompanying the retraction published Wednesday, Nature stated that the all co-authors of both the papers had finally concluded that they cannot stand behind the papers, and have decided to retract them. The editorial also stated that the episode disclosed flaws in Natures procedures, and expressed the need to move quality assurance higher up on its agenda.

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"Acid Bath Stem Cell" Breakthrough Debunked, Nature Retracts Papers

PUBLIC RELEASE DATE:

2-Jul-2014

Contact: Kristina Grifantini press@salk.edu Salk Institute

LA JOLLA-Researchers around the world have turned to stem cells, which have the potential to develop into any cell type in the body, for potential regenerative and disease therapeutics.

Now, for the first time, researchers at the Salk Institute, with collaborators from Oregon Health & Science University and the University of California, San Diego, have shown that stem cells created using two different methods are far from identical. The finding could lead to improved avenues for developing stem cell therapies as well as a better understanding of the basic biology of stem cells.

The researchers discovered that stem cells created by moving genetic material from a skin cell into an empty egg cell-rather than coaxing adult cells back to their embryonic state by artificially turning on a small number of genes-more closely resemble human embryonic stem cells, which are considered the gold standard in the field.

"These cells created using eggs' cytoplasm have fewer reprogramming issues, fewer alterations in gene expression levels and are closer to real embryonic stem cells," says co-senior author Joseph R. Ecker, professor and director of Salk's Genomic Analysis Laboratory and co-director of the Center of Excellence for Stem Cell Genomics. The results of the study were published today in Nature.

Human embryonic stem cells (hESCs) are directly pulled from unused embryos discarded from in-vitro fertilization, but ethical and logistical quandaries have restricted their access. In the United States, federal funds have limited the use of hESCs so researchers have turned to other methods to create stem cells. Most commonly, scientists create induced pluripotent stem (iPS) cells by starting with adult cells (often from the skin) and adding a mixture of genes that, when expressed, regress the cells to a pluripotent stem-cell state. Researchers can then coax the new stem cells to develop into cells that resemble those in the brain or in the heart, giving scientists a valuable model for studying human disease in the lab.

Over the past year, a team at OHSU built upon a technique called somatic cell nuclear transfer (the same that is used for cloning an organism, such as Dolly the sheep) to transplant the DNA-containing nucleus of a skin cell into an empty human egg, which then naturally matures into a group of stem cells.

Ecker, holder of the Salk International Council Chair in Genetics, teamed up with Shoukhrat Mitalipov, developer of the new technique and director of the Center for Embryonic Cell and Gene Therapy at OHSU, and UCSD assistant professor Louise Laurent to carry out the first direct comparison of the two approaches. The scientists created four lines of nuclear transfer stem cells all using eggs from a single donor, along with seven lines of iPS cells and two lines of the gold standard hESCs. All cell lines were shown to be able to develop into multiple cell types and had nearly identical DNA content contained within them.

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Some stem cell methods closer to 'gold standard' than others

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Newswise A team of researchers from the University of California, San Diego School of Medicine, Oregon Health & Science University (OHSU) and Salk Institute for Biological Studies has shown for the first time that stem cells created using different methods produce differing cells. The findings, published in the July 2, 2014 online issue of Nature, provide new insights into the basic biology of stem cells and could ultimately lead to improved stem cell therapies.

Capable of developing into any cell type, pluripotent stem cells offer great promise as the basis for emerging cell transplantation therapies that address a wide array of diseases and conditions, from diabetes and Alzheimers disease to cancer and spinal cord injuries. In theory, stem cells could be created and programmed to replace ailing or absent cells for every organ in the human body.

The gold standard is human embryonic stem cells (ES cells) cultured from discarded embryos generated by in vitro fertilization, but their use has long been limited by ethical and logistical considerations. Scientists have instead turned to two other methods to create stem cells: Somatic cell nuclear transfer (SCNT), in which genetic material from an adult cell is transferred into an empty egg cell, and induced pluripotent stem cells (iPS cells), in which adult cells are reverted back to a stem cell state by artificially turning on targeted genes.

Until now, no one had directly and closely compared the stem cells acquired using these two methods. The scientists found they produced measurably different results. The nuclear transfer ES cells are much more similar to real ES cells than the iPS cells, said co-senior author Louise Laurent, PhD, assistant professor in the Department of Reproductive Medicine at UC San Diego. They are more completely reprogrammed and have fewer alterations in gene expression and DNA methylation levels that are attributable to the reprogramming process itself.

The development and use of iPS cells has grown exponentially in recent years, in no small part due to the fact that they can be generated from adult cells (often from the skin) by temporarily turning on a combination of four genes to induce the adult cells to return to a pluripotent state.

Laurent noted that iPS cell lines have been created from patients to model many different diseases and the ability to make personalized iPS cells from a patient that could be transplanted back into that patient has generated excitement because it would eliminate the need for immunosuppression.

The nuclear transfer method has been pioneered more recently by a team led by Shoukhrat Mitalipov, PhD, professor and director of the Center for Embryonic Cell and Gene Therapy at OSHU. The technique is similar to the process used in cloning, but the pluripotent cells are collected from early embryos before they develop into mature organisms.

For their comparisons, the researchers at UC San Diego, OSHU and Salk created four nuclear transfer ES cell lines and seven iPS cell lines using the same skin cells as the source of donor genetic material, then compared them to two standard human ES lines. All 13 cell lines were shown to be pluripotent using a battery of standard tests.

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New Reprogramming Method Makes Better Stem Cells

On a brilliant day in April, tens of thousands of baseball fans stream past Jonathan Thomas's office towards AT&T Park for the first home game of the San Francisco Giants 2014 season. Thomas's standing desk faces away from the window, but the cheering throngs are never far from his mind.

Thomas chairs the board of the California Institute for Regenerative Medicine (CIRM), the US$3-billion agency hailed by scientists around the world for setting a benchmark for stem-cell research funding. But scientists will not be the ones who decide what becomes of CIRM when the cash runs out in 2017. Instead, it will be the orange-and-black-clad masses walking past Thomas's window. And to win their support, Thomas knows that the agency needs to prove that their collective investment has been worthwhile. We need to drive as many projects to the patient as soon as possible, he says.

Californians voted CIRM into existence in 2004, making it the largest funder of stem-cell work in the world. The money the proceeds of bond sales that must be repaid with $3 billion in interest by taxpayers helped to bring 130 scientists to the state, and created several thousand jobs there. It has funded research that led to the publication of more than 1,700 papers, and it has contributed to five early clinical trials.

The institute has navigated a difficult path, however. CIRM had to revamp its structure and practices in response to complaints about inefficiency and potential conflicts of interest. It has also had to adapt its mission to seismic shifts in stem-cell science.

Now, ten years after taking off, the agency is fighting for its future. It has a new president, businessman Randal Mills, who replaces biologist Alan Trounson. Its backers have begun to chart a course for once again reaching out to voters, this time for $5 billion (with another $5 billion in interest) in 2016. And it is under intense pressure to produce results that truly matter to the public.

Whether or not CIRM succeeds, it will serve as a test bed for innovative approaches to funding. It could be a model for moving technologies to patients when conventional funding sources are not interested.

Much of what is celebrated and lamented about CIRM can be traced back to the Palo Alto real-estate developer who conceived of it: Robert Klein. Although officially retired from CIRM he chaired the board from 2004 to 2011 (see 'State of funding') Klein's office is adorned with mementos of the agency: a commemorative shovel from the groundbreaking of a CIRM-funded stem-cell research centre, and a photo of him with former governor Arnold Schwarzenegger at the ribbon-cutting ceremony.

Liz Hafalia/San Francisco Chronicle/Polaris/eyevine

Patient advocates and parents at a 2012 meeting in which US$100 million in CIRM grants were approved.

It was Klein's idea to ask voters to support stem-cell research in 2004, through a ballot measure called Proposition 71. When he succeeded, CIRM instilled a kind of euphoria in stem-cell scientists, who were at the time still reeling from a 2001 decree by then-President George W. Bush that severely limited federal funding for embryonic-stem-cell research. California's commitment removed this roadblock and revealed that many in the state and the country supported the research.

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Stem cells: Hope on the line

Salk Institute scientist Joseph Ecker holds a flow cell slide used in a genome sequencing machine. Ecker and colleagues compared the genomes of two kinds of artificial embryonic stem cells for a study comparing their quality.

In a setback for hopes of therapy with a promising kind of artificial embryonic stem cells, a study published in the journal Nature has found that these "induced pluripotent stem cells" have serious quality issues.

However, scientists who performed the study, including researchers from the Salk Institute and UC San Diego, say it should be possible to improve the quality of these IPS cells. They say lessons can be learned from studying a newer technique of making human embryonic stem cells through nuclear transfer, the same technology used to create Dolly the cloned sheep.

In addition, the study does not prove that the quality problems will affect therapy with the cells, said scientists who examined the study. That remains to be tested.

The IPS cells are made from skin cells treated with "reprogramming" factors that turn back the clock, so they very closely resemble embryonic stem cells. The hope is that these IPS cells could be differentiated into cells that can repair injuries or relieve diseases. Because they can be made from a patient's own cells, the cells are genetically matched, reducing worries of immune rejection.

In San Diego, scientists led by Jeanne Loring at The Scripps Research Institute have created IPS cells from the skin cells of Parkinson's disease patients, and turned the IPS cells into neurons that produce dopamine. They hope to get approval next year to implant these cells into the patients, relieving symptoms for many years. The project is online under the name Summit4StemCell.org.

A major concern is that IPS cells display abnormal patterns of gene activation and repression. This is controlled by a process called methylation. This process adds chemicals called methyl groups to DNA, but these "epigenetic" changes do not change the underlying DNA sequence. Methylation represses gene function; removing the methyl groups, or demethylation, activates them.

The Nature study was led by Shoukhrat Mitalipov of Oregon Health & Scence University. Mitalipov made headlines last year for applying nuclear transfer to derive human embryonic stem cells, the first time this has been achieved in human cells. These cells can be made to be a near-perfect genetic match to the patient, and their quality closely resembles those of true embryonic stem cells.

"We know that the embryonic stem cells are the gold standard, and we've been always trying to make patient-matched cells that would match the gold standard," Mitalipov said. "And at this point it looks like the NT (nuclear transfer) cells produce exactly those cells that would be best."

Nuclear transfer involves placing a nucleus from a skin cell into an egg cell that has had its nucleus removed. The cell is then stimulated, and starts dividing in the same way a fertilized egg cell divides to form an embryo.

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Artificial embryonic stem cells have quality problems: study

July 3, 2014

redOrbit Staff & Wire Reports Your Universe Online

A new process known as somatic cell nuclear transfer is far better and much more accurate when it comes to coaxing embryonic stem cells out of human skin tissue, according to new research appearing in Tuesdays edition of the journal Nature.

Scientists from Oregon Health & Science University (OHSU), the University of California-San Diego (UCSD) School of Medicine and the Salk Institute for Biological Studies created stem cells using two different methods: nuclear transfer, which involves moving genetic material from a skin cell into an empty egg cell, and a more traditional method in which activating a small number of genes reverts adults cells back to an embryonic state.

Experts believe that stem cell therapies could someday be used to replace human cells damaged through injury or illness, including spinal cord injuries, diabetes, Parkinsons disease and multiple sclerosis. Human embryonic stem cells (ES cells), which are cells cultured from discarded embryos, are viewed by scientists as the gold standard of the field, and the new study reports that somatic cell nuclear transfer (SCNT) more closely resembled ES cells.

This marks the first time that researchers had directly compared the SCNT method with the induced pluripotent stem cell (iPS cell) technique, and in a statement, co-senior author and UCSD assistant professor in reproductive medicine Dr. Louise Laurent explained that the nuclear transfer ES cells were more completely reprogrammed and had fewer alterations in gene expression and DNA methylation levels than the iPS cells.

Access to actual human embryonic stem cells (hESCs) has been limited in the US due to ethical and logistical issues, forcing researchers to devise other methods to create stem cells, the study authors explained. Typically, that means creating iPS cells by taking adult cells and adding in a mixture of genes that regress those cells to a pluripotent stem-cell state. Those cells can then be coaxed into cells resembling those found in the heart or brain.

Over the past year, however, an OHSU-led team of researchers have built upon somatic cell nuclear transfer (the same technique used for cloning organisms) to transplant the DNA-containing nucleus of a skin cell into an empty human egg. Once completed, the combination naturally matures into a group of stem cells.

For the first time, the OHSU, UCSD and Salk Institute researchers conducted a direct, in-depth comparison of the two different methods. They created four nuclear transfer ES cell lines and seven iPS cell lines using the same skin cells as the donor genetic material source, and then compared them to a pair of standard human ES lines.

A battery of standard tests revealed that all 13 cell lines were shown to be pluripotent. However, when the researchers used powerful genomic techniques to take a closer look at the DNA methylation (a biochemical process responsible for turning genes on or off) and the gene expression signatures of each cell line, they discovered that the nuclear transfer ES cells more closely resembled those of ES cells than did iPS cells in both characteristics.

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Nuclear Transfer Proven An Effective Method In Stem Cell Production

When an aging Hollywood action star or sex symbol reemerges after a long hiatus looking younger, with a great body and smoother, firmer facial skin, people now assume they have undergone stem cell therapy.

In my interview with doctors Eric and Anna Yalung of Regenestem Manila, they set me straight. While the actor/actress may have had stem cell therapy, the outward appearance is most likely a combination of Botox, plastic surgery, a strict diet and a personal trainer. So no doctor who only offers you stem cell can promise you outwardly beautifying results.

This is not to say though that there are no beauty benefits from it. For the beauty aspect, they do this for facial skin rejuvenation and hair growth. According to head dermatologist Anna Yalung, they inject the target area and, if necessary, combine it with services available at the clinic for best results and to speed up the process.

Shots are spaced a week to a month apart depending on treatment requirement for three sessions. The follow-up is scheduled the following year.

How is it done? Platelet Rich Plasma (PRP) is a convenient and cell-based treatment. It is a simple procedure involving the extraction of blood, separation of platelets and administering the PRP to the desired area.

This is done in order to stimulate or promote healing, collagen synthesis for anti-aging, or to deliver proper oxygenation to muscles or tissues. A crucially important function of platelets is the release of various growth factors responsible for almost all repair processes that occur in the body.

Dr. Eric Yalung, who has conducted PRP treatments with Dr. Joseph Purita, world-renowned pioneer in stem cell orthopedic surgery, will spearhead PRP therapy for arthritis, sports injuries, anti-aging, hair growth, facial rejuvenation and pain management. Yalung clears that it is not a cure-all. It wont make you thinner or outwardly younger by itself. Its main purpose is improving the quality of ones life and the highest success rates are for those who are suffering from osteoarthritis; degenerative diseases like diabetes, multiple sclerosis, Parkinsons and Alzheimers; sports injuries and pain management.

Regenestems team of four physicians do not work with embryonic stem cells, only with adult stem cells. Adult stem cells are found in all tissues of the growing human being and, according to latest reports, also have the potential to transform themselves into practically all other cell types, or revert to being stem cells with greater reproductive capacity.

The clinic also provides the option for patient treatments in Regenestem clinics worldwide (US, Mexico, Argentina, and Dubai), and includes assistance in hotel and travel plans.

Regenestem Manila is at 2/F, Belson House, 271 Edsa, Mandaluyong City; tel. 2452200. Visit http://www.regenestemasia.com

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Can stem cells really restore your youthful looks?

This image provided by the National Institutes of Health shows red blood cells in a patient with sickle cell disease at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

This image provided by the National Institutes of Health shows red blood cells in a different sickle cell patient, after a bone marrow transplant at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results seen with a similar technique used in children.

The researchers and others say the findings show age need not be a barrier and that the technique may change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were even able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening; patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, with hopes that the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

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Bone marrow transplants can reverse adult sickle cell disease

PUBLIC RELEASE DATE:

1-Jul-2014

Contact: Krysten Carrera krysten.carrera@nih.gov 301-435-8112 The JAMA Network Journals

Use of a lower intensity bone marrow transplantation method showed promising results among 30 patients (16-65 years of age) with severe sickle cell disease, according to a study in the July 2 issue of JAMA.

Myeloablative (use of high-dose chemotherapy or radiation) allogeneic hematopoietic stem cell transplantation (HSCT; receipt of hematopoietic stem cells "bone marrow" from another individual) is curative for children with severe sickle cell disease, but associated toxicity has made the procedure prohibitive for adults. The development of nonmyeloablative conditioning regimens (use of lower doses of chemotherapy or radiation to prepare the bone marrow to receive new cells) may facilitate safer application of allogeneic HSCT to eligible adults, according to background information in the article.

Matthew M. Hsieh, M.D., of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md., and colleagues explored a nonmyeloablative approach in a pilot group of 10 adults with severe sickle cell disease, using a simplified HSCT regimen (with stem cell donation from a immunologically matched sibling), that had few toxic effects, yet all patients continued taking immunosuppression medication. The researchers have since revised the protocol to include an option to stop immunosuppression after 1 year in selected patients (those with donor CD3 engraftment of greater than 50 percent and normalization of hemoglobin). In this report, the authors describe the outcomes for 20 additional patients with severe sickle cell disease, along with updated results from the first 10 patients. All 30 patients (ages 16-65 years) were enrolled in the study from July 2004 to October 2013.

As of October 25, 2013, 29 patients were alive with a median follow-up of 3.4 years, and 26 patients (87 percent) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. Hemoglobin levels improved after HSCT; at 1 year, 25 patients (83 percent) had full donor-type hemoglobin. Fifteen engrafted patients discontinued immunosuppression medication and had no graft-vs-host disease.

The average annual hospitalization rate was 3.2 the year before HSCT, 0.63 the first year after, 0.19 the second year after, and 0.11 the third year after transplant. Eleven patients were taking narcotics long-term at the time of transplant. During the week they were hospitalized and received their HSCT, the average narcotics use per week was 639 mg of intravenous morphine-equivalent dose. The dosage decreased to 140 mg 6 months after the transplant.

There were 38 serious adverse events including pain, infections, abdominal events, and toxic effects from the medication sirolimus.

"In this article, we extend our previous results and show that this HSCT procedure can be applied to older adults, even those with severe comorbid conditions " the authors write. "These data reinforce the low toxicity of this regimen, especially among patients with significant end-organ dysfunction."

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Bone marrow transplantation shows potential for treating adults with sickle cell disease

Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results from a similar technique used in children.

The researchers and others say the findings show that age need not be a barrier and that the technique could change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

Sickle cell disease is a genetic condition that damages oxygen-carrying hemoglobin in red blood cells that then form sickle shapes that can block blood flow through veins. It can cause anemia, pain and organ damage. The disease affects about 100,000 Americans and millions worldwide.

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening. Patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, hoping the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

Results from the adult study, involving patients aged 29 on average, were published Tuesday in the Journal of the American Medical Association.

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Study finds new treatment for adult sickle cell disease

UVA joins National Marrow Donor Program giving greater access to cancer treatments by Ishaan Sachdeva | Jun 25 2014 | 06/25/14 10:11pm | Updated 14 hours ago

The Emily Couric Cancer Center of the University of Virginia Health System has expanded its access to bone marrow and hematopoietic stem cell transplant donors. Now designated as a National Marrow Donor Program (NMDP), the Health System will have access to the Be The Match Registry, the worlds largest and most diverse bone marrow registry. Implications of this change are significant for patients afflicted with blood cancers like leukemia who obtain treatment through the Health System.

Bone marrow, the soft, spongy tissue within bones like the sternum or the ilium of the pelvis, forms hematopoietic or blood-forming stem cells. These cells, unlike embryonic stem cells, differentiate only into types of blood cells- red blood cells, white blood cells or clotting platelets. Leukemia causes bone marrow to produce abnormal, leukemic white blood cells that divide uncontrollably, forming tumors that deprive cells of oxygen and reduce infection defense. One treatment method is autologous bone marrow transplant, in which patients receive stem cells from their healthy, non cancerous bone marrow.

The idea [of autologous transplants] is that you extract healthier bone marrow from the patient to have a source of stored, non-cancerous bone marrow. You can then treat the patient with higher doses of treatment than you can normally give because the most common limitation to treatment is that treatment will kill off healthy bone marrow you might have, said Thomas P. Loughran Jr., MD, the Universitys Cancer Center director.

Essentially, a patients healthy bone marrow is safeguarded outside their body while aggressive treatment is administered to kill cancerous marrow. Another form of treatment is allogeneic treatment, in which bone marrow is transplanted from a sibling or an unrelated donor.

In an allogeneic transplant, you are also transplanting in a new immune system. The new immune system comes in and recognizes the body as a foreign tissue and starts attacking that tissue. This causes a beneficial graft vs. leukemia effect where this new immune system attacks any residual leukemia, but may also cause a harmful graft versus host disease where normal tissue is also attacked, Loughran said.

The donor and recipient tissue interaction underscores the genetic component of bone marrow transplants from external donors. Despite the curative potential of a bone marrow transplant, a strong genetic match between donor and recipient is crucial to the utility of a transplant.

The ability of any donor to be successful is based on genetics. Its called HLA [human leukocyte antigen] typing. The HLA system has four genes called A, B, C and D, and it turns out that A, B and D are influential. We have half of our genes each from both parents, so we have six of these: 2 A, 2 B and 2 D. The best case is a six out of six match from a brother or sister, but the chances are only 1 in 4, said Loughran. The consequence of low genetic probabilities is a large pool of unrelated donors, like the Be The Match Registry. Through such services, patients have a greater chance of finding an unrelated donor who may provide a successful genetic match.

The coordinating center would identify the place where the donor is living and tell them they are potentially able to donate. In the past, the donor would have bone marrow directly extracted. Now it is almost always from the PBSCT [peripheral blood stem cell transplantation] procedure. The donor takes a growth factor that stimulates growth of the needed hematopoietic stem cells within their peripheral blood circulation. A catheter collects this blood and the stem cells are separated from the blood by a machine, and the blood is returned back to the donor. The collected stem cells are sent to the lab where they are purified and frozen, Loughran said.

Meanwhile, the patient in preparation for the transplant is given the highest dose of chemotherapy that can be tolerated. The donated stem cells are administered to the patient in a way similar to IV fluid.

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UVA Expands Cancer Treatment

The treatment could edge out joint replacement procedures to a large extent.

Hyderabad, June 30:

A team of doctors from a city hospital have harvested stem cells of a person using bone marrow from the pelvis area to replace some dead tissues in the hip. By doing this, they saved the patient from undergoing a hip replacement.

The Apollo Health City team, headed by orthopaedic specialist Paripati Sharat Kumar, diagnosed a 39-year-old women suffering from Avascular Necrosis. Her condition would require undergoing a replacement of hips.

After assessing her condition, the team has decided to go for the autologous stem cell procedure (where donor and the receiver is the same person) to save both the hip joints.

The minimally invasive procedure involved taking bone marrow aspirate from the patients pelvis. Stem cells were harvested from the aspirate through a process that takes about 15 minutes. Stems cells were planted in the area of damage under fluoroscopy control following core decompression, Kumar said in a statement on Monday.

He feels that the autologous stem cell treatment could edge out joint replacement procedures to a large extent in the days to come. The scope of this procedure in orthopaedics and sports medicine is enormous. This could be extended to indications including osteoarthritis of knee, shoulder, hip, elbows, ankle and spine, he said.

(This article was published on June 30, 2014)

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Autologous stem cell treatment could be the road ahead

In the second part of our series on the need for bone marrow donors, NY1's Erin Billups takes a look at what goes into donating bone marrow and some of the lingering misconceptions.

Following the death of their colleague, Marlon Layne, members of the marketing firm Ogilvy & Mather started a campaign to get the word out about the prevalence of blood cancers and the need for more diversity within the donor pool.

Over the past three years they've raised nearly $42,000 for the cause and signed up around 160 new donors to the Be the Match Registry.

"I cant change the past but I can ensure that in the future nobody else like Marlon has to be waiting for a marrow registrant from somebody whos of their same race," says Ogilvy & Mather Marketing Analytics Associate Director Omari Jinaki.

Omari Jinaki says he has noticed a level of hesitancy to participate within the black community, though.

"That is rooted, clearly, in hundreds of years of history of being misguided and misrepresented and underrepresented by the systems that are supposed to protect us," Jinaki says.

There's also a lack of awareness of the need within the Latino and Asian communities, and lingering misconceptions the donation process.

Many believe it's painful, with significant recovery time.

"The process has changed in the way one donates bone marrow. Seventy-five percent of the time, it's just like a blood donation," says Icla Da Silva Foundation President Airam Da Silva.

Depending on the recipient's need, most can now donate via a peripheral blood stem cell, or PBSC.

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Misconceptions Keep Bone Marrow Registry from Attracting Diverse Donor Pool

20 hours ago Forty-two hours after they began to differentiate, embryonic cells are clearly segregating into endoderm (red), mesoderm (blue) and ectoderm (black). Researchers say the key to achieving this patterning in culture is confining the colonies geometrically. Credit: Brivanlou Lab, The Rockefeller University

About seven days after conception, something remarkable occurs in the clump of cells that will eventually become a new human being. They start to specialize. They take on characteristics that begin to hint at their ultimate fate as part of the skin, brain, muscle or any of the roughly 200 cell types that exist in people, and they start to form distinct layers.

Although scientists have studied this process in animals, and have tried to coax human embryonic stem cells into taking shape by flooding them with chemical signals, until now the process has not been successfully replicated in the lab. But researchers led by Ali Brivanlou, Robert and Harriet Heilbrunn Professor and head of the Laboratory of Stem Cell Biology and Molecular Embryology at The Rockefeller University, have done it, and it turns out that the missing ingredient is geometrical, not chemical.

"Understanding what happens in this moment, when individual members of this mass of embryonic stem cells begin to specialize for the very first time and organize themselves into layers, will be a key to harnessing the promise of regenerative medicine," Brivanlou says. "It brings us closer to the possibility of replacement organs grown in petri dishes and wounds that can be swiftly healed."

In the uterus, human embryonic stem cells receive chemical cues from the surrounding tissue that signal them to begin forming layersa process called gastrulation. Cells in the center begin to form ectoderm, the brain and skin of the embryo, while those migrating to the outside become mesoderm and endoderm, destined to become muscle and blood and many of the major organs, respectively.

Brivanlou and his colleagues, including postdocs Aryeh Warmflash and Benoit Sorre as well as Eric Siggia, Viola Ward Brinning and Elbert Calhoun Brinning Professor and head of the Laboratory of Theoretical Condensed Matter Physics, confined human embryonic stem cells originally derived at Rockefeller to tiny circular patterns on glass plates that had been chemically treated to form "micropatterns" that prevent the colonies from expanding outside a specific radius. When the researchers introduced chemical signals spurring the cells to begin gastrulation, they found the colonies that were geometrically confined in this way proceeded to form endoderm, mesoderm and ectoderm and began to organize themselves just as they would have under natural conditions. Cells that were not confined did not.

By monitoring specific molecular pathways the human cells use to communicate with one another to form patterns during gastrulationsomething that was not previously possible because of the lack of a suitable laboratory modelthe researchers also learned how specific inhibitory signals generated in response to the initial chemical cues function to prevent the cells within a colony from all following the same developmental path.

The research was published June 29 in Nature Methods.

"At the fundamental level, what we have developed is a new model to explore how human embryonic stem cells first differentiate into separate populations with a very reproducible spatial order just as in an embryo," says Warmflash. "We can now follow individual cells in real time in order to find out what makes them specialize, and we can begin to ask questions about the underlying genetics of this process."

The research also has direct implications for biologists working to create "pure" populations of specific cells, or engineered tissues consisting of multiple cell types, for use in medical treatments. "These cells have a powerful intrinsic tendency to form patterns as they develop," Warmflash says. "Varying the geometry of the colonies may turn out to be an important tool that can be used to guide stem cells to form specific cell types or tissues."

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Using geometry, researchers coax human embryonic stem cells to organize themselves

Miami (PRWEB) July 01, 2014

Global Stem Cells Group announced the grand opening of Regenestem Asia in Manila, Philippines, adding a new state-of-the-art clinic to the international stem cell medicine company's growing worldwide presence. With clinics in Miami, New York, Los Angeles and Dubai, Regenestem Asia now offers the same comprehensive stem cell treatments and experienced medical staff that have fueled the company's worldwide growth.

The launch of Regenestem Asia is a collaborative effort between Global Stem Cells Group and Eric Yalung, M.D. of the Cosmetic Surgery Institute-Manila, Inc., a prominent plastic surgeon committed to taking stem cell medicine, research and practice in the Philippines to a world-class level. The first Regenestem brand clinic in the Philippines, Regenestem Asia is a 22,000 square foot facility with a focus on offering the most advanced protocols in cosmetic cellular medicine to patients from around the world.

Under Yalung's leadership as Regenestem Medical Director, patients will receive the latest and least-invasive techniques in Stem Cell medicine available. Yalung is joined by a team of talented stem cell specialists to provide world-class patient treatment and follow-up care under the Regenestem brand.

In addition to cosmetic treatments, Regenestem offers stem cell treatments for arthritis, autism, chronic obstructive pulmonary disease (COPD), diabetes and multiple sclerosis among many other medical conditions at various facilities worldwide.

As part of its commitment to maintaining the highest standards in service and technology, Regenestem Asia provides an international staff experienced in administering the leading cellular therapies available.

Like all Regenestem facilities, Regenestem Asia is certified for the medical tourism market, and staff physicians are board-certified or board-eligible. Regenestem clinics provide services in more than 10 specialties, attracting patients from the United States and around the world.

For more information, visit the Regenestem website, email bnovas(at)regenestem(dot)com or call 305-224-1858.

About Regenestem:

Regenestem is a division of the Global Stem Cells Group, Inc., is an international medical practice association committed to researching and producing comprehensive stem cell treatments for patients worldwide. Having assembled a highly qualified staff of medical specialists-professionals trained in the latest cutting-edge techniques in cellular medicine-Regenestem continues to be a leader in delivering the latest protocols in the adult stem cell arena.

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Global Stem Cells Group Subsidiary Regenestem Announces Grand Opening of State-of-the-Art Regenestem Asia Stem Cell ...