Author Archives: admin


Stem Cell Clinic > Articles by: admin

Artificial embryonic stem cells have quality problems: study

By Stem Cell Medical Center

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.

Read more here:
Artificial embryonic stem cells have quality problems: study

Nuclear Transfer Proven An Effective Method In Stem Cell Production

By Uncategorized

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.

View original post here:
Nuclear Transfer Proven An Effective Method In Stem Cell Production

ARTIFICIAL EMBRYONIC STEM CELL QUALITY IMPAIRED: STUDY

By Stem Cell Treatment

In a setback for a promising kind of therapy based on artificial embryonic stem cells, a study published Wednesday in the journal Nature has found that they have serious quality issues.

Scientists who conducted the study, including those from the Salk Institute and UC San Diego in La Jolla, said it should be possible to improve the quality of these cells, which are called induced pluripotent stem cells. They said lessons can be learned from a technique of making 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 actually affect the envisioned therapy, said scientists who examined it. That remains to be tested.

Induced pluripotent stem cells, called IPS cells for short, 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 IPS cells could be turned into cells that can repair injuries or relieve diseases. Because they can be made from a patients own cells, IPS cells are genetically matched, reducing worries of rejection by a persons immune system.

In San Diego, scientists led by Jeanne Loring at The Scripps Research Institute have created IPS cells from the extracted skin cells of Parkinsons disease patients and turned those IPS cells into neurons that produce dopamine. They hope to get federal approval next year to implant the customized cells back into the patients and see whether the treatment is effective.

A major concern is that IPS cells display abnormal patterns of gene activation and repression. This is controlled by a process called methylation, which adds molecules called methyl groups to DNA. Methylation represses genes, while removing the methyl groups, or demethylation, activates them.

The Nature study was led by Shoukhrat Mitalipov of Oregon Health & Science University. Mitalipov made headlines last year for using nuclear transfer to derive human embryonic stem cells, the first time this has been achieved. Cells produced through this method can form 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 weve been always trying to make patient-matched cells that would match the gold standard, Mitalipov said. And at this point, it looks like the (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 it starts dividing in the same way a fertilized egg cell divides to form an embryo.

The new study found that when compared with the IPS cell method, nuclear transfer yields stem cells that much more closely resemble natural embryonic stem cells.

View original post here:
ARTIFICIAL EMBRYONIC STEM CELL QUALITY IMPAIRED: STUDY

Less Toxic Transplant Treatment Offers Hope for Sickle Cell Patients

By Stem Cell Treatment

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.

The rest is here:
Less Toxic Transplant Treatment Offers Hope for Sickle Cell Patients

SICKLE CELL DISEASE REVERSED WITH STEM CELL TRANSPLANTS

By Stem Cell Treatment

A stem cell transplant reversed sickle cell disease in adults, according to a study that offers a potential cure for the debilitating condition.

Half of those who had the transplant, which involved a combination of the patients stem cells and those of a sibling, also were able to stop taking immunosuppressant drugs without experiencing rejection or having the donor cells attack their body, research released Tuesday in the Journal of the American Medical Association showed. People undergoing stem cell transplants usually must take immunosuppressants for the rest of their lives.

More than 90,000 people in the U.S. have sickle cell disease, a genetic disorder found mostly in people of African descent, according to the U.S. National Institutes of Health. The condition can cause severe pain, organ damage and stroke. Study author Matthew Hsieh said its too soon to say the researchers have found a cure, as patients have been followed only for an average of 3 years, but he is optimistic.

Theyre sickle-cell free for now, said Hsieh, a staff clinician at the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute in Bethesda, Md. We are cautiously optimistic they are cured.

Children with sickle cell disease can receive a transplant that combines chemotherapy with stem cells, he said. Adults, though, are usually considered too sick for that treatment.

Follow this link:
SICKLE CELL DISEASE REVERSED WITH STEM CELL TRANSPLANTS

Science journal retracts paper on stem cell discovery

By Stell Cell Research

Karen Weintraub, Special for USA TODAY 3:14 p.m. EDT July 2, 2014

Riken researcher Haruko Obokata announces Jan. 28, 2014, that she discovered a simple way to turn animal cells back to a youthful, neutral state, a feat hailed as a "game-changer" in the quest to grow transplant tissue in the lab. The journal Nature announced it is retracting the research paper.(Photo: Jiji Press, AFP/Getty Images)

The scientific journal Nature Wednesday retracted two stem cell papers that received national attention when they were published in January.

The paper by researchers from Harvard University and Japan's RIKEN Institute described a new method of producing versatile stem cells without altering their DNA a process that promised to make it easier to use stem cells in research and treatment.

Stem cell researchers immediately raised questions about these new cells, called STAP cells, and have tried unsuccessfully for months to reproduce the process of making the cells, as described by the papers.

One author, Teruhiko Wakayama from RIKEN, has been calling since March for a retraction in light of the concerns. The first author, Haruko Obokata, a junior scientist at RIKEN, was accused by her institution in April of scientific misconduct after errors were found in the images, and some of the descriptions in the paper were found to be plagiarized.

Harvard stem cell and tissue engineering biologist Charles Vacanti, who helped lead the research and was the last of the authors to call for a retraction, said Wednesday that he still believes in the existence of STAP cells but can no longer stand behind the papers.

"Although there has been no information that cast doubt on the existence of the stimulus-triggered acquisition of pluripotency (STAP) cell phenomenon itself, I am concerned that the multiple errors that have been identified impair the credibility of the manuscript as a whole," he said in a prepared statement.

Stem cells have long been seen as the future of medical care, offering the possibility of mending damaged hearts, replacing brain cells lost to Alzheimer's or repairing paralyzed spinal cords. But that potential has been limited first by the controversial need to destroy embryos for research, then by the cumbersome and expensive techniques used to make stem cells without embryos.

In the January papers in Nature, researchers showed they could turn mature cells into STAP cells cheaply and easily, essentially by bathing skin or other cells in acid..

Read this article:
Science journal retracts paper on stem cell discovery

Stem cells: Hope on the line : Nature News & Comment

By Stell Cell Research

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.

More:
Stem cells: Hope on the line : Nature News & Comment

Scientists Withdraw Report on Simpler Stem Cells – ABC News

By Stell Cell Research

U.S. and Japanese scientists who reported that they'd found a startlingly simple way to make stem cells withdrew that claim Wednesday, admitting to "extensive" errors in the research.

In two papers published in January in the journal Nature, the researchers said that they'd been able to transform ordinary mouse cells into versatile stem cells by exposing them to a mildly acidic environment. Someday, scientists hope to harness stem cells to grow replacement tissue for treating a variety of diseases.

While researchers have long been able to perform such transformations with a different method, the newly reported technique was far simpler, and the papers caused a sensation and some skepticism in the research community. They were also widely reported in the media, including by The Associated Press.

But before long, the government-funded Riken Center for Developmental Biology in Japan accused one of its scientists, Haruko Obokata, of falsifying data in the research. Obokata, the key author of the papers, defended the results during a televised news conference in April while apologizing for using wrong and altered images in the published reports. She also said she opposed withdrawing the papers, a process called retraction, and the 30-year-old attributed her mistakes to inexperience.

On Wednesday, Nature released a statement from Obokata and the other authors of the papers that retracted the papers, a rare occurrence for the prestigious journal. The scientists acknowledged "extensive" errors that meant "we are unable to say without a doubt" that the method works. They noted that studies of the simpler method are still going on by other researchers.

The Riken center also said on its website Wednesday that it expected a separate statement from Obokata and would post it when available.

Dr. Charles Vacanti of the Harvard-affiliated Brigham and Women's Hospital in Boston, another main author, issued his own statement in which he said he believes the further studies will vindicate the method, which produced what the authors called STAP cells.

But another author, Yoshiki Sasai, deputy director of the Riken center, said the errors in the papers meant "it has become increasingly difficult to call the STAP phenomenon even a promising hypothesis." In a statement issued by Riken, he said he was "deeply ashamed" of the problems in the papers.

The Riken investigation that led to allegations against Obokata also focused on Sasai and two other employees, but they were not accused of research misconduct.

Retractions of papers in major scientific journals like Nature are unusual. They can come about because of fraud or the discovery of honest mistakes that undercut the conclusions of research. Publications like Nature routinely have experts review papers submitted by scientists to look for problems. But in an editorial released Wednesday, Nature concluded that its editors and reviewers "could not have detected the fatal faults in this work."

Read the original:
Scientists Withdraw Report on Simpler Stem Cells - ABC News

Bone marrow transplants can reverse adult sickle cell disease

By Stem Cell Doctors

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.

Originally posted here:
Bone marrow transplants can reverse adult sickle cell disease

Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

1-Jul-2014

Contact: Krysten Carrera NIDDKMedia@mail.nih.gov 301-496-3583 NIH/National Institute of Diabetes and Digestive and Kidney Diseases

Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease NIH trial success suggests a new treatment option for older, sicker patients

Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Health's Clinical Center in Bethesda, Maryland, by researchers from NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.

The transplant done in the study reversed sickle cell disease in nearly all the patients. Despite having both donor stem-cells and their own cells in their blood, the patients stopped the immunosuppressant medication without experiencing rejection or graft-versus-host disease, in which donor cells attack the recipient. Both are common, serious side effects of transplants.

"Typically, stem-cell recipients must take immunosuppressants all their lives," said Matthew Hsieh, M.D., lead author on the paper and staff clinician at NIH. "That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen."

In sickle cell disease (SCD) sickle-shaped cells block blood flow. It can cause severe pain, organ damage and stroke. The only cure is a blood stem-cell, or bone marrow, transplant. The partial transplant performed in the study is much less toxic than the standard "full" transplant, which uses high doses of chemotherapy to kill all of the patient's marrow before replacing it with donor marrow. Several patients in the study had less than half of their marrow replaced.

Immunosuppressant medication reduces immune system strength and can cause serious side effects such as infection and joint swelling. In this study, 15 of 30 adults stopped taking the medication under careful supervision one year after transplant and still had not experienced rejection or graft-versus-host disease at a median follow up of 3.4 years.

"Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease," said John F. Tisdale, M.D., the paper's senior author and a senior investigator at NIH. "Not having to permanently rely on this medication, along with use of the relatively less-toxic partial stem-cell transplant, means that even older patients and those with severe sickle cell disease may be able to reverse their condition."

See the original post here:
Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease

→←