Ordinary cells turned into stem cells 'game-changing'

Japanese scientists say they have developed a new process to make stem cells that is simpler and faster than current methods. Sarah Toms reports.

EMBRYONIC FORM: A mouse embryo formed with Stimulus-Triggered Acquisition of Pluripotency (STAP) cells.

BREAKTHROUGH: Stimulus-Triggered Acquisition of Pluripotency (STAP) cells.

In experiments that could open a new era in stem cell biology, scientists have found a simple way to change mature animal cells back into an embryonic-like state that allows them to generate many types of tissue.

The research, described as game-changing by experts in the field, suggests human cells could in future be reprogrammed by the same technique, offering a simpler way to replace damaged cells or grow new organs for sick and injured people.

Chris Mason, chair of regenerative medicine bioprocessing at University College London, who was not involved in the work, said its approach in mice was "the most simple, lowest-cost and quickest method" to generate so-called pluripotent cells - able to develop into many different cell types - from mature cells.

"If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material - the age of personalised medicine would have finally arrived," he said.

The experiments, reported in two papers in the journal Nature this week, involved scientists from the RIKEN Center for Developmental Biology in Japan and Brigham and Women's Hospital and Harvard Medical School in the United States.

The researchers took skin and blood cells, let them multiply, then subjected them to stress "almost to the point of death", they explained, by exposing them to various events including trauma, low oxygen levels and acidic environments.

One of these "stressful" situations was simply to bathe the cells in a weak acid solution for around 30 minutes.

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Ordinary cells turned into stem cells 'game-changing'

Scientists report making stem cells in about 30 minutes

In a feat that experts say is a significant advance for regenerative medicine, scientists have discovered a surprisingly simple method for creating personalized stem cells that doesnt involve human embryos or tinkering with DNA.

Two studies published Wednesday in the journal Nature describe a novel procedure for reprogramming the blood cells of newborn mice by soaking the cells in a mildly acidic solution for 30 minutes. This near-fatal shock caused the cells to become pluripotent, or capable of growing into any type of cell in the body.

When the reprogrammed cells were tagged and injected into a developing mouse, they multiplied and grew into heart, bone, brain and other organs, the scientists found.

It was really surprising to see that such a remarkable transformation could be triggered simply by stimuli from outside of the cell, said lead study author Haruko Obokata, a biochemistry researcher at the RIKEN research institute in Japan. Very surprising.

The simplicity of the technique, which Obokata and her colleagues dubbed stimulus triggered acquisition of pluripotency, or STAP, caught many experts off-guard.

So you mistreat cells under the right conditions and they assume a different state of differentiation? Its remarkable, said Rudolf Jaenisch, a pioneering stem cell researcher at MIT who was not involved in the study. Lets see whether it works in human cells, and theres no reason why it shouldnt.

Obokata said that researchers had already begun experiments on human cells, but offered no details.

VIDEO: A beating heart, grown from STAP stem cells

Due to their Zelig-like ability to form any number of specialized cells, pluripotent stem cells are considered the basic building blocks of biology. Scientists are working on ways to use them to repair severed spinal cords, replace diseased organs, and treat conditions as varied as diabetes, blindness and muscular dystrophy.

By using stem cells spawned from the patients own cells, replacement tissues would stand less of a chance of being attacked by the patients own immune system, researchers say. That would spare patients the need to undergo a lifetime regimen of dangerous, immune-suppressing drugs.

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Scientists report making stem cells in about 30 minutes

Screening for transformed human mesenchymal stromal cells with tumorigenic potential

PUBLIC RELEASE DATE:

29-Jan-2014

Contact: Dr. Qiuwei Pan q.pan@erasmusmc.nl Society for Experimental Biology and Medicine

Researchers at Erasmus University Medical Center Rotterdam, The Netherlands, led by Dr. Qiuwei Pan and Dr. Luc van der Laan, have discovered that spontaneous tumorigenic transformation of human mesenchymal stem/stromal cells (MSCs) can occur during cell culture expansion, although the frequency is relatively low and often only observed after extensive passage in culture. This report appears in the January 2014 issue of Experimental Biology and Medicine.

Currently, MSCs are being widely investigated as a potential treatment for various diseases. According to ClinicalTrials.gov, over 350 clinical trials using MSCs have been registered by the end of 2013 (with a search of: mesenchymal stem cells). For cell transplantation, MSCs are often isolated from either the patient or from a third party donor, and then expanded in cell culture before therapeutic application. In fact, spontaneous transformation of primary cells in cell culture has been well-investigated over decades. Malignant transformation of murine and monkey MSCs has also recently been reported.

The current study confirmed that spontaneous tumorigenic transformation of human MSCs can occur during cell culture expansion. This potentially has large implications for the clinical application of ex vivo expanded MSCs. "Although this transformation is rare, we do need to carefully examine the presence of these aberrant cells in MSC cultures, before transplanting into patients", stresses the first author Dr. Pan. "We now have identified RNA molecule signatures that can be applied as a potential biomarker for the detection of these dangerous cells in long-term cultures", said senior author Dr. van der Laan. "However, further research is required to validate this biomarker in clinical grade cultures of MSCs that are used in clinical trials".

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "This study provides a possible method for testing the safety of expanded adult stem cells. We look forward to the validation of these RNA biomarkers".

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Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit http://www.sebm.org. If you are interested in publishing in the journal please visit http://ebm.sagepub.com/.

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Screening for transformed human mesenchymal stromal cells with tumorigenic potential

Stem cell timeline: The history of a medical sensation

Stem cells are the cellular putty from which all tissues of the body are made. Ever since human embryonic stem cells were first grown in the lab, researchers have dreamed of using them to repair damaged tissue or create new organs, but such medical uses have also attracted controversy. Yesterday, the potential of stem cells to revolutionise medicine got a huge boost with news of an ultra-versatile kind of stem cell from adult mouse cells using a remarkably simple method. This timeline takes you through the ups and downs of the stem cell rollercoaster.

1981, Mouse beginnings Martin Evans of Cardiff University, UK, then at the University of Cambridge, is first to identify embryonic stem cells in mice.

1997, Dolly the sheep Ian Wilmut and his colleagues at the Roslin Institute, Edinburgh unveil Dolly the sheep, the first artificial animal clone. The process involves fusing a sheep egg with an udder cell and implanting the resulting hybrids into a surrogate mother sheep. Researchers speculate that similar hybrids made by fusing human embryonic stem cells with adult cells from a particular person could be used to create genetically matched tissue and organs.

1998, Stem cells go human James Thomson of the University of Wisconsin in Madison and John Gearhart of Johns Hopkins University in Baltimore, respectively, isolate human embryonic stem cells and grow them in the lab.

2001, Bush controversy US president George W. Bush limits federal funding of research on human embryonic stem cells because a human embryo is destroyed in the process. But Bush does allow continued research on human embryonic stem cells lines that were created before the restrictions were announced.

2005, Fraudulent clones Woo Suk Hwang of Seoul National University in South Korea reports that his team has used therapeutic cloning a technique inspired by the one used to create Dolly to create human embryonic stem cells genetically matched to specific people. Later that year, his claims turn out to be false.

2006, Cells reprogrammed Shinya Yamanaka of Kyoto University in Japan reveals a way of making embryonic-like cells from adult cells avoiding the need to destroy an embryo. His team reprograms ordinary adult cells by inserting four key genes forming "induced pluripotent stem cells".

2007, Nobel prize Evans shares the Nobel prize for medicine with Mario Capecchi and Oliver Smithies for work on genetics and embryonic stem cells.

2009, Obama-power President Barack Obama lifts 2001 restrictions on federal funding for human embryonic stem cell research.

2010, Spinal injury A person with spinal injury becomes the first to receive a medical treatment derived from human embryonic stem cells as part of a trial by Geron of Menlo Park, California, a pioneering company for human embryonic stem cell therapies.

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Stem cell timeline: The history of a medical sensation

Scientists hail stem cell breakthrough

In experiments that could open a new era in stem cell biology, scientists have found a simple way to reprogramme mature animal cells back into an embryonic-like state that allows them to generate many types of tissue.

The research, described as game-changing by experts in the field, suggests human cells could in future be reprogrammed by the same technique, offering a simpler way to replace damaged cells or grow new organs for sick and injured people.

Chris Mason, chair of regenerative medicine bioprocessing at University College London, who was not involved in the work, said its approach in mice was "the most simple, lowest-cost and quickest method" to generate so-called pluripotent cells - able to develop into many different cell types - from mature cells.

"If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material - the age of personalised medicine would have finally arrived," he said.

The experiments, reported in two papers in the journal Nature on Wednesday, involved scientists from the RIKEN Center for Developmental Biology in Japan and Brigham and Women's Hospital and Harvard Medical School in the United States.

The researchers took skin and blood cells, let them multiply, then subjected them to stress "almost to the point of death", they explained, by exposing them to various events including trauma, low oxygen levels and acidic environments.

One of these "stressful" situations was simply to bathe the cells in a weak acid solution for around 30 minutes.

Within days, the scientists found that the cells had not only survived but had also recovered by naturally reverting into a state similar to that of an embryonic stem cell.

These stem cells - dubbed Stimulus-Triggered Acquisition of Pluripotency, or STAP, cells by the researchers - were then able to differentiate and mature into different types of cells and tissue, depending on the environments they were put in.

"NEW ERA"

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Scientists hail stem cell breakthrough

Converting Adult Human Cells to Hair-Follicle-Generating Stem Cells

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Newswise PHILADELPHIA - If the content of many a situation comedy, not to mention late-night TV advertisements, is to be believed, theres an epidemic of balding men, and an intense desire to fix their follicular deficiencies.

One potential approach to reversing hair loss uses stem cells to regenerate the missing or dying hair follicles. But it hasnt been possible to generate sufficient number of hair-follicle-generating stem cells until now.

Xiaowei George Xu, MD, PhD, associate professor of Pathology and Laboratory Medicine and Dermatology at the Perelman School of Medicine, University of Pennsylvania, and colleagues published in Nature Communications a method for converting adult cells into epithelial stem cells (EpSCs), the first time anyone has achieved this in either humans or mice.

The epithelial stem cells, when implanted into immunocompromised mice, regenerated the different cell types of human skin and hair follicles, and even produced structurally recognizable hair shaft, raising the possibility that they may eventually enable hair regeneration in people.

Xu and his team, which includes researchers from Penns departments of Dermatology and Biology, as well as the New Jersey Institute of Technology, started with human skin cells called dermal fibroblasts. By adding three genes, they converted those cells into induced pluripotent stem cells (iPSCs), which have the capability to differentiate into any cell types in the body. They then converted the iPS cells into epithelial stem cells, normally found at the bulge of hair follicles.

Starting with procedures other research teams had previously worked out to convert iPSCs into keratinocytes, Xus team demonstrated that by carefully controlling the timing of the growth factors the cells received, they could force the iPSCs to generate large numbers of epithelial stem cells. In the Xu study, the teams protocol succeeded in turning over 25% of the iPSCs into epithelial stem cells in 18 days. Those cells were then purified using the proteins they expressed on their surfaces.

Comparison of the gene expression patterns of the human iPSC-derived epithelial stem cells with epithelial stem cells obtained from human hair follicles showed that the team had succeeded in producing the cells they set out to make in the first place. When they mixed those cells with mouse follicular inductive dermal cells and grafted them onto the skin of immunodeficient mice, they produced functional human epidermis (the outermost layers of skin cells) and follicles structurally similar to human hair follicles.

This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, Xu says. And those cells have many potential applications, he adds, including wound healing, cosmetics, and hair regeneration.

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Converting Adult Human Cells to Hair-Follicle-Generating Stem Cells

Medical breakthrough Cord Blood Center opening in Oklahoma

Posted on: 1:16 pm, January 28, 2014, by Ashley Kringen and KFOR-TV, updated on: 05:37pm, January 28, 2014

Oklahoma City, Okla.-Families at the OU Med Center have the opportunity to help save lives by donating umbilical cord blood, to be used as a source of life for people battling leukemia and other blood disorders.

There are only 24 cord blood centers worldwide and this is the first in Oklahoma.

Dr. James Smith with the Oklahoma Blood Institute said, Were really hoping to be able to meet a very special need.

Each year thousands of people are diagnosed with blood cancers or other blood diseases.

For some, the only hope of a cure is a marrow transplant.

Umbilical cord blood can be used as an alternative to supply those needs.

The goal for Oklahomas Cord Blood Center is to focus on the minority population.

Dr. Smith said Vastly underrepresented in terms of having cord blood or even stem cell donations that are available for transplants.

Mothers would have the option of donating their babys umbilical cord, rather than just throwing it away.

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Medical breakthrough Cord Blood Center opening in Oklahoma

New method increases supply of embryonic stem cells

15 hours ago

A new method allows for large-scale generation of human embryonic stem cells of high clinical quality. It also allows for production of such cells without destroying any human embryos. The discovery is a big step forward for stem cell research and for the high hopes for replacing damaged cells and thereby curing serious illnesses such as diabetes and Parkinson's disease.

Currently human embryonic stem cells are made from surplus in vitro fertilized (IVF) embryos that are not used for the generation of pregnancies. The embryos do not survive the procedure. Therefore it has been illegal in the USA to to use this method for deriving embryonic stem cell lines. Sweden's legislation has been more permissive. It has been possible to generate embryonic stem cells from excess, early IVF embryos with the permission of the persons donating their eggs and sperm.

An international research team led by Karl Tryggvason, Professor of Medical Chemistry at Karolinska Institutet in Sweden and Professor at Duke-NUS Graduate Medical School in Singapore has, together with Professor Outi Hovatta at Karolinska Institutet, developed a method that makes it possible to use a single cell from an embryo of eight cells. This embryo can then be re-frozen and, theoretically, be placed in a woman's uterus. The method is already used in Pre-implantation Genetic Diagnosis (PGD) analyses, where a genetic test is carried out on a single cell of an IVF embryo in order to detect potential hereditary diseases. If mutations are are not detected, the embryo is inserted in the woman's uterus, where it can grow into a healthy child.

"We know that an embryo can survive the removal of a single cell. This makes a great ethical difference," says Karl Tryggvason.

The single stem cell is then cultivated on a bed of a human laminin protein known as LN-521 that is normally associated with pluripotent stem cells in the embryo. This allows the stem cell to duplicate and multiply without being contaminated. Previously the cultivation of stem cells has been done on proteins from animals or on human cells, which have contaminated the stem cells through uninhibited production of thousands of proteins.

"We can cultivate the stem cells in a chemically defined, clinical quality environment. This means that one can produce stem cells on a large scale, with the precision required for pharmaceutical production," says Karl Tryggvason.

Embryonic stem cells are pluripotent and can develop into any kind of cell. This means that they can become dopamine producing cells, insulin producing cells, heart muscle cells or eye cells, to name but a few of the hopes placed on cell therapy using stem cells.

"Using this technology the supply of human embryonic stem cells is no longer a problem. It will be possible to establish a bank where stem cells can be matched by tissue type, which is important for avoiding transplants being rejected," says Karl Tryggvason.

Explore further: Stem cells on the road to specialization

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New method increases supply of embryonic stem cells

California to fund research in stem-cell genomics

SACRAMENTO, Calif. (AP) The state of California is preparing to invest up to $40 million in a new scientific field that backers say could revolutionize medicine and lead to personalized medical treatments.

The directors of the California Institute for Regenerative Medicine are meeting in Berkeley this Wednesday to create one or two research centers for stem-cell genomics, the Sacramento Bee (http://bit.ly/1mKZTRp) reported Sunday.

Scientists and biotech companies in the San Francisco Bay Area, San Diego and elsewhere are competing for the research money.

Researchers believe that genomics, the study of genes and their relationships, can lead to more effective therapies that are tailored to a patient's genetic makeup.

The new research centers for stem-cell genomics could help make California a leader in the fast-moving field.

"Right now, in a lot of ways, doctors are making educated guesses as to how to treat us patients more generally," said UC Davis stem cell researcher Paul Knoepfler. "By knowing our genomic information ... they could be making far more educated choices about treatments."

The move into genomics comes as the California Institute for Regenerative Medicine struggles to fulfill the promises of the 2004 ballot initiative campaign that created the $3 billion stem-cell agency.

So far, no new therapies have emerged from the state institute, which will run out of cash for new awards in less than three years and needs some high-profile success to raise more money.

Two years ago, the stem cell agency decided to move ahead with the plan to fund research into stem-cell genomics and began accepting applications for research money.

A group headed by Stanford University's Michael Snyder, director of its Center for Genomics and Personalized Medicine, is expected to receive a $33 million award, based on documents posted Friday on the agency's website.

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California to fund research in stem-cell genomics

Audio-Digest Foundation Announces the Release of Oncology Volume 04, Issue 22: What’s New in Breast Cancer?

Glendale, CA (PRWEB) January 26, 2014

Audio-Digest Foundation Announces the Release of Oncology Volume 04, Issue 22: Whats New in Breast Cancer?

The goal of this program is to improve the management of breast cancer. After hearing and assimilating this program, the clinician will be better able to:

1. Recognize the role of cancer stem cells and their microenvironment in the development and recurrence of breast cancer. 2. List components of the stem cell compartment and microenvironment that promote the development of breast cancer. 3. Explain a proposed mechanism by which cancer stem cells may maintain their stemness. 4. Select patients most likely to benefit from prolonged tamoxifen therapy. 5. Weigh the benefits and risks of newer breast cancer therapies.

The original programs were presented by Issam Makhoul, MD, Assistant Professor, Division of Hematology/Oncology, Department of Internal Medicine, and University of Arkansas for Medical Sciences, College of Medicine, Little Rock.

Audio-Digest Foundation, the largest independent publisher of Continuing Medical Education in the world, records over 10,000 hours of lectures every year in anesthesiology, emergency medicine, family practice, gastroenterology, general surgery, internal medicine, neurology, obstetrics/gynecology, oncology, ophthalmology, orthopaedics, otolaryngology, pediatrics, psychology, and urology, by the leading medical researchers at the top laboratories, universities, and institutions.

Recent researchers have hailed from Harvard, Cedars-Sinai, Mayo Clinic, UCSF, The University of Chicago Pritzker School of Medicine, The University of Kansas Medical Center, The University of California, San Diego, The University of Wisconsin School of Medicine, The University of California, San Francisco, School of Medicine, Johns Hopkins University School of Medicine, and many others.

Out of these cutting-edge programs, Audio-Digest then chooses the most clinically relevant, edits them for clarity, and publishes them either every week or every two weeks.

In addition, Audio-Digest publishes subscription series in conjunction with leading medical societies: DiabetesInsight with The American Diabetes Association, ACCEL with The American College of Cardiology, Continuum Audio with The American Academy of Neurology, and Journal Watch Audio General Medicine with Massachusetts Medical Society.

For 60 years, the global medical community of doctors, nurses, physician assistants, and other medical professionals around the world has subscribed to Audio-Digest specialty series in order to remain current in their specialties as well as to maintain their Continuing Education requirements with the most cutting-edge, independent, and unbiased continuing medical education (CME).

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Audio-Digest Foundation Announces the Release of Oncology Volume 04, Issue 22: What’s New in Breast Cancer?