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Brave cancer battler Ulrika in race against time to find stem cell donor

By Stem Cell Doctors

Brave Ulrika Dandekar needs a life saver.

The 21-year-old from Solihull was given the devastating news she had a rare type of blood cancer, called Anaplastic Lymphoma, just just three months ago.

And she knows without a stem cell transplant she will not survive.

Now a desperate search has been launched for a donor but the odds are stacked against Ulrika, with just one in 125,000 likelihood of finding a match because of her Asian background.

Her emotional plea for help comes at the start of National Transplant Week on Monday.

When you are in my position, desperately in need of a donor, and you are told the statistics its devastating, said Ulrika, who had dreams of becoming a doctor.

I have a six per cent chance of surviving. When I found this out I couldnt stop crying... you start wondering whether you will get better.

You hear your parents talking about your cancer to friends and how its growing faster than the drugs are working.

I am a 21-year-old who should be out studying, working, partying, holidaying and discovering myself. But Im not. Instead I am struggling, crying, hurting, forever waiting.

Solihull cancer patient Ulrika Dandeka

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Brave cancer battler Ulrika in race against time to find stem cell donor

Can stem cells really restore your youthful looks?

By Stem Cell Treatment

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?

Special Harvard Commentary: How Stem Cells Help Treat Human Disease

By Stem Cell Doctors

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

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

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