Stem Cell Clinic

Schizophrenia-associated gene variation affects brain cell development

By Stem Cell Medicine

PUBLIC RELEASE DATE:

3-Jul-2014

Contact: Shawna Williams shawna@jhmi.edu 410-955-8236 Johns Hopkins Medicine

Johns Hopkins researchers have begun to connect the dots between a schizophrenia-linked genetic variation and its effect on the developing brain. As they report July 3 in the journal Cell Stem Cell, their experiments show that the loss of a particular gene alters the skeletons of developing brain cells, which in turn disrupts the orderly layers those cells would normally form.

"This is an important step toward understanding what physically happens in the developing brain that puts people at risk of schizophrenia," says Guo-li Ming, M.D., Ph.D., a professor of neurology and neuroscience in the Johns Hopkins University School of Medicine's Institute for Cell Engineering.

While no single genetic mutation is known to cause schizophrenia, so-called genomewide association studies have identified variations that are more common in people with the condition than in the general population. One of these is a missing piece from an area of the genome labeled 15q11.2. "While the deletion is linked to schizophrenia, having extra copies of this part of the genome raises the risk of autism," notes Ming.

For the new study, Ming's research group, along with that of her husband and collaborator, neurology and neuroscience professor Hongjun Song, Ph.D., used skin cells from people with schizophrenia who were missing part of 15q11.2 on one of their chromosomes. (Because everyone carries two copies of their genome, the patients each had an intact copy of 15q11.2 as well.)

The researchers grew the human skin cells in a dish and coaxed them to become induced pluripotent stem cells, and then to form neural progenitor cells, a kind of stem cell found in the developing brain.

"Normally, neural progenitors will form orderly rings when grown in a dish, but those with the deletion didn't," Ming says. To find out which of the four known genes in the missing piece of the genome were responsible for the change, the researchers engineered groups of progenitors that each produced less protein than normal from one of the suspect genes. The crucial ingredient in ring formation turned out to be a gene called CYFIP1.

The team then altered the genomes of neural progenitors in mouse embryos so that they made less of the protein created by CYFIP1. The brain cells of the fetal mice turned out to have similar defects in structure to those in the dish-grown human cells. The reason, the team found, is that CYFIP1 plays a role in building the skeleton that gives shape to each cell, and its loss affects spots called adherens junctions where the skeletons of two neighboring cells connect.

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Schizophrenia-associated gene variation affects brain cell development

Nature STAP stem cell studies retracted after more errors found

By Stem Cell Medicine

Following months of controversy, editors at the scientific journal Nature have retracted two high-profile studies that purported to demonstrate a quick and simple way of making flexible stem cells without destroying embryos or tinkering with DNA.

Several critical errors have been found in our Article and Letter, Nature wrote in a retraction statement issued Wednesday. We apologize for the mistakes.

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FOR THE RECORD

July 3, 7:53 a.m.: An article in the July 3 A section about two controversial stem cell studies that were retracted had stated that the decision was made by editors at the journal Nature. The retraction decision was made by the authors of the studies. Additionally, the comments in the retraction statement should have been attributed to the authors of the studies, not to the journal editors.

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The two reports described a new way of reprogramming blood cells so that they would revert to a developmentally primitive state and be capable of growing into any type of cell. Researchers from Japan and the United States said they accomplished this feat by soaking the cells in an acid bath for 30 minutes and then spinning them in a centrifuge for 5 minutes.

The resulting stem cells dubbed stimulus triggered acquisition of pluripotency, or STAP had the hallmarks of embryonic stem cells. When the researchers injected them into developing mice, the STAP stem cells grew into heart, bone and brain cells, among others, the research team reported in January.

Scientists in the field of regenerative medicine were giddy at the prospect of using the cells to grow new insulin-producing cells for people with Type 1 diabetes or central nervous system cells for people with spinal cord injuries, to name a few examples. Since these replacement tissues would be generated from a patients own cells, researchers believed they would not prompt the immune system to attack, eliminating the need for patients to take immune-suppressing drugs.

But it didnt take long for some researchers to suspect that STAP stem cells were too good to be true. Critiques posted online gained more currency when labs began reporting that they werent able to replicate the experiments. Then one of the senior researchers who worked on both of the studies called for the papers to be withdrawn until the results could be independently verified.

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Nature STAP stem cell studies retracted after more errors found

Stem cell type resists chemotherapy drug

By Stem Cell Medical Center

A new study shows that adipose-derived human stem cells, which can become vital tissues such as bone, may be highly resistant to the common chemotherapy drug methotrexate (MTX). The preliminary finding from lab testing may prove significant because MTX causes bone tissue damage in many patients.

MTX is used to treat cancers including acute lymphoblastic leukemia, the most common form of childhood cancer. A major side effect of the therapy, however, is a loss of bone mineral density. Other bone building stem cells, such as bone marrow derived stem cells, have not withstood MTX doses well.

"Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs," said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. "That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldn't have these issues."

Stem cell survivors

Originally Beane was doing much more basic research. She was looking for chemicals that could help purify adipose-derived stem cells (ASCs) from mixed cell cultures to encourage their proliferation. Among other things, she she tried chemotherapy drugs, figuring that maybe the ASCs would withstand a drug that other cells could not. The idea that this could help cancer patients did not come until later.

In the study published online in the journal Experimental Cell Research, Beane exposed pure human ASC cultures, "stromal vascular fraction" (SVF) tissue samples (which include several cell types including ASCs), and cultures of human fibroblast cells, to medically relevant concentrations of chemotherapy drugs for 24 hours. Then she measured how those cell populations fared over the next 10 days. She also measured the ability of MTX-exposed ASCs, both alone and in SVF, to proliferate and turn into other tissues.

Beane worked with co-authors fellow center member Eric Darling, the Manning Assistant Professor in the Department of Molecular Pharmacology, Physiology and Biotechnology, and research assistant Vera Fonseca.

They observed that three chemotherapy drugs -- cytarabine, etoposide, and vincristine -- decimated all three groups of cells, but in contrast to the fibroblast controls, the ASCs withstood a variety of doses of MTX exceptionally well (they resisted vincristine somewhat, too). MTX had little or no effect on ASC viability, cell division, senescence, or their ability to become bone, fat, or cartilage tissue when induced to do so.

The SVF tissue samples also withstood MTX doses well. That turns out to be significant, Darling said, because that's the kind of tissue that would actually be clinically useful if an ASC-based therapy were ever developed for cancer patients. Hypothetically, fresh SVF could be harvested from the fat of a donor, as it was for the study, and injected into bone tissue, delivering ASCs to the site.

To understand why the ASCs resist MTX, the researchers conducted further tests. MTX shuts down DNA biosynthesis by binding the protein dihydrofolate reductase so that it is unavailable to assist in that essential task. The testing showed that ASCs ramped up dihydrofolate reductase levels upon exposure to the drug, meaning they produced enough to overcome a clinically relevant dose of MTX.

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Stem cell type resists chemotherapy drug

"Stress-Induced" Stem Cell Findings Are Retracted

By Stem Cell Medical Center

High-profile reports claiming an easy way to create pluripotent cells were flawed.

The controversial work involved a mouse embryo injected with cells made pluripotent through stress. Credit: Haruko Obokata

Naturetoday retracted two controversial papers on stem cells that it published in January. The retractions agreed to by all of the co-authors come at the end of a whirlwind five months during which various errors were spotted in the papers, attempts to replicate the experiments failed, the lead author was found guilty of misconduct, and the centre where she is employed was threatened with dismantlement. The retraction noticeincludes a handful of problems with the papers that had not been previously considered by institutional investigation teams.

Questions remain over what exactly was the basis for claims that embryonic-like stem cells could be created by exposing bodily cells to stress a technology the authors called stimulus-triggered acquisition of pluripotency, orSTAP. But the controversy promises to have lasting impact on science in Japan, global stem-cell research, and the scientific community more broadly including changes in editorial policy at Nature. AnEditorial posted todaywith the retractions notes the need for improvements in publishing procedures: The episode has further highlighted flaws inNatures procedures and in the procedures of institutions that publish with us. (Natures news and comment team is editorially independent of its research editorial team.)

The first of the two papersdescribed a method of using acid exposure or physical pressure to convert spleen cells from newborn mice into pluripotent cells cells that can become any cell in the body. The second paperfurther impressed stem-cell scientists with data showing that the STAP process created cells that could differentiate into placenta cells, something that other pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, do not normally do.

But within weeks, duplicated and manipulated images were discovered, focusing attention on the source of data provided by Haruko Obokata, a biochemist at the RIKEN Center for Developmental Biology in Kobe and first author on both papers. Scientists also reported difficulties in replicating the experiments.

A RIKEN investigation team looking into the papers announced on April 1 that Obokata had been foundguilty of two counts of scientific misconduct. RIKENrejected an appeal, and advised her to retract the papers in May. Co-author Teruhiko Wakayama of the University of Yamanishi had been arguing for retraction since March.

Obokata and Charles Vacanti, an anaesthesiologist at the Brigham and Womens Hospital in Boston, Massachusetts, and the senior corresponding author on the first article, both stood by its claims, but later changed their positions after new errors emerged. Obokatagave her consent to the retraction of both paperson June 4.

The retraction notice published today lists five new errors. The first four note that captions do not describe what is in the corresponding images or figures, without reflecting on how this relates to the experimental data. The fifth, relating to the first paper, notes that purported STAP cells are of a different genetic background from those supposedly used in the experiments something it calls inexplicable discrepancies.

The notice concludes: These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC [stem cell] phenomenon is real.

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"Stress-Induced" Stem Cell Findings Are Retracted

Research integrity: Cell-induced stress

By Stem Cell Medical Center

Kimimasa Mayama/EPA/Alamy

Haruko Obokata tearfully faces the media after she was found guilty of misconduct in April.

It seemed almost too good to be true and it was. Two papers1, 2 that offered a major breakthrough in stem-cell biology were retracted on 2 July, mired in a controversy that has damaged the reputation of several Japanese researchers.

For scientists worldwide it has triggered painful memories of a decade-old scandal. In February 2004, South Korean researcher WooSuk Hwang announced that he had generated stem-cell lines from cloned human embryos3, creating a potential source of versatile, therapeutic cells that would be genetically matched to any patient. A frenzy of excitement followed this and a subsequent publication4, but that didnt compare with the media firestorm when the results were revealed to be fabricated. The two main cloning papers were retracted5, and the careers of some dozen scientists were devastated.

In the soul-searching that followed, research integrity became a hot topic, scientists re-evaluated the responsibilities of authorship, and institutions vowed to improve the way that they police their staff. Nature and other journals also made promises, saying that they would vet manuscripts more thoroughly. In an Editorial at the time, Nature wrote6: Keeping in mind the principle that extraordinary claims require extraordinary proof, Nature may in rare cases demand it.

A year later, when Shoukhrat Mitalipov of the Oregon Health & Science University in Portland claimed to have cloned embryonic-stem-cell lines from monkeys7, Nature required independent tests to verify that the lines came from the monkey donors. This verification was published alongside the cloning paper8. I applaud what they did, says Alan Trounson, the outgoing president of the California Institute for Regenerative Medicine in San Francisco, who helped with the testing.

Then came Japans stem-cell case. This January, Haruko Obokata, a young biochemist at the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan, reported in Nature1, 2 that she had converted mouse cells to an embryonic-like state merely by subjecting them to stress, such as physical pressure or exposure to acid (see Nature 505, 596; 2014). The process, labelled stimulus-triggered acquisition of pluripotency (STAP), was so contrary to current thinking that some scientists said they accepted it based only on the reputation of Obokatas co-authors, who were some of the most trusted names in stem-cell research and cloning.

But the paper1 that set out the fundamental technique was soon shot full of holes. There was plagiarized text in the article. Figures showed signs of manipulation, and some images were identical or nearly identical to those used later in the same paper and elsewhere to represent different experiments. More damning were genetic analyses that strongly suggested the cells were not what they were purported to be. And although deriving STAP cells was advertised as simple and straightforward, no one has yet been able to repeat the experiment.

Within the space of six months, Obokata was found guilty of misconduct by her institution; well-respected scientists, including RIKEN head Ryoji Noyori, bowed their heads in apology; and both papers were retracted9. In the end, the evidence for STAP cells seemed so flimsy that observers began to ask where were the extra precautions and the extraordinary proof that had been promised post-Hwang.

The case has reopened difficult questions about the quality of research and peer review, and the responsibilities of co-authors, institutions and journals. It is also making its mark as an example of how not to do things. The episode has already become a parable in my lab for teaching students about scientific ethics, says Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California.

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Research integrity: Cell-induced stress

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

By Stem Cell Medical Center

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

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.

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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.

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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.

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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.

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Less Toxic Transplant Treatment Offers Hope for Sickle Cell Patients

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