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Animal-free reprogramming of adult cells improves safety

20 hours ago Growing stem cells in conditions free of animal material makes them safe for use in humans. Credit: Eraxion/iStock/Thinkstock

Human stem cells produced through genetic reprogramming are beset by safety concerns because current techniques alter the DNA of the stem cells and use material from animals to grow them. Now, A*STAR researchers have developed an efficient approach that produces safe, patient-specific human stem cells.

Human induced pluripotent stem cells have the potential to treat a number of diseases without the ethical issues associated with embryonic stem cells. Pluripotent stem cells can be produced from adult cells by introducing genes that reprogram them. Typically, the stem cells are grown on a layer of mouse cells in solutions (known as media) that contain animal proteinsand therefore, potentially may also carry disease. For such stem cells to be safe for use in humans, they need to be grown in 'xeno-free' conditions, which are devoid of material from other animals.

Andrew Wan and Hong Fang Lu at the A*STAR Institute of Bioengineering and Nanotechnology in Singapore and colleagues set out to develop a new xeno-free system. The researchers carried out the genetic reprogramming of cells on an artificially produced protein substrate rather than mouse cells. They also used media that contained no animal components. The result was more efficient reprogramming than seen with conventional approaches.

"A xeno-free system will eliminate the risk of disease transmission from other species, which is important for regulatory approval," explains Wan. "Yet there have been few studies on cell reprogramming under totally xeno-free conditions."

The researchers went one step further by addressing the problem of cells acquiring alterations to their DNA during reprogramming.

"Incorporation of transgenes into the genome of the cell poses another safety issue, risking unwanted genetic alterations," explains Lu. "In our work, the transgenes were introduced to initiate the reprogramming, but after this they were removed from the cell, leading to transgene-free stem cells."

The researchers demonstrated that after genetic reprogramming and the removal of the added genes, the stem cells could still develop into different cells types. They were even able to induce them to form dopaminergic neurons, the type that degenerates in Parkinson's disease. The conditions in which the stem cells were grown mean that they are suitable for clinical use and can be derived from a patient's own cells, ensuring complete compatibility.

"Regulatory approval for clinical application of stem cells largely depends on the conditions in which the stem cells are derived," says Wan. "We present a workable protocol for the reprogramming of fibroblasts to stem cells that minimizes any potential safety risks."

Explore further: Discovery may make it easier to develop life-saving stem cells

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Animal-free reprogramming of adult cells improves safety

Cell discovery brings blood disorder cure closer

PUBLIC RELEASE DATE:

13-Aug-2014

Contact: Lucy Handford media@monash.edu Monash University

A cure for a range of blood disorders and immune diseases is in sight, according to scientists who have unravelled the mystery of stem cell generation.

The Australian study, led by researchers at the Australian Regenerative Medicine Institute (ARMI) at Monash University and the Garvan Institute of Medical Research, is published today in Nature. It identifies for the first time mechanisms in the body that trigger hematopoietic stem cell (HSC) production.

Found in the bone marrow and in umbilical cord blood, HSCs are critically important because they can replenish the body's supply of blood cells. Leukemia patients have been successfully treated using HSC transplants, but medical experts believe blood stem cells have the potential to be used more widely.

Lead researcher Professor Peter Currie, from ARMI explained that understanding how HSCs self-renew to replenish blood cells is a "Holy Grail" of stem cell biology.

"HSCs are one of the best therapeutic tools at our disposal because they can make any blood cell in the body. Potentially we could use these cells in many more ways than current transplantation strategies to treat serious blood disorders and diseases, but only if we can figure out how they are generated in the first place. Our study brings this possibility a step closer," he said.

A key stumbling block to using HSCs more widely has been an inability to produce them in the laboratory setting. The reason for this, suggested from previous research, is that a molecular 'switch' may also be necessary for HSC formation, though the mechanism responsible has remained a mystery, until now.

In this latest study, ARMI researchers observed cells in the developing zebra fish - a tropical freshwater fish known for its regenerative abilities and optically clear embryos - to gather new information on the signalling process responsible for HSC generation.

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Cell discovery brings blood disorder cure closer

Stem cell discovery: Australian scientists make significant find while studying zebrafish

Australian scientists studying zebrafish have stumbled upon what they say is one of the most significant discoveries in stem cell research.

In research published on Thursday in the journal Nature, the Monash University scientists revealed that they uncovered how one of the most important stem cells in blood and bone marrow, the haematopoietic stem cell (HSC), is formed.

Professor Peter Currie, from Monash University's Australian Regenerative Medicine Institute, said the discovery brought researchers closer to growing HSCs in a lab.

"HSCs are the basis of bone marrow transplantations as a therapy, so when a leukaemia patient receives bone marrow, it's really these HSCs that do the heavy lifting," Professor Currie said.

"So when clinicians do bone marrow transplants, they need to find a matching donor recipients and we know that's a hit or miss procedure.

"So for many years people have been trying to make HSCs in the dish, and they've had very little success in doing this."

Professor Currie, who led the study, said the discovery brought scientists much closer to achieving that aim.

"It's the discovery of a completely new cell type that basically is required to give instructions to the HSC to make it become what it needs to become," he said.

"It means we now understand how HSC form in the body better, we can use that information to try to grow these cells in the dish and we hope that will lead to better treatment for people with leukaemia and blood disorders."

Professor Currie said he specialises in muscle stem cell biology and accidentally came across the discovery while studying muscle stem cells in zebrafish.

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Stem cell discovery: Australian scientists make significant find while studying zebrafish

Cellular Dynamics reports higher quarterly revenues and bigger losses

Cellular Dynamics International said revenues for the quarter that ended June 30 rose nearly 30 percent over the same quarter last year but expenses jumped even more quickly.

The Madison stem cell company reported a net loss of $8.6 million, or 54 cents a share, on $3.6 million in revenues for the most recent quarter compared with a $5.1 million net loss, or $2.92 a share, on revenues of $2.8 million for the same period last year.

Costs rose because of higher research and development expenses related to CDI's contract to set up a stem cell bank with the California Institute for Regenerative Medicine, San Francisco, and to higher expenses resulting from CDI's initial public stock offering in July 2013, the company said.

At the same time, CDI said, it has manufactured stem cells for 179 customers in the past 12 months, up from 136 customers in the previous year, and the largest customers increased their purchases by 45 percent.

"We intend to achieve profitability in the long term," said the company, which was founded in 2004 by UW-Madison stem cell pioneer James Thomson.

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Cellular Dynamics reports higher quarterly revenues and bigger losses

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WASHINGTON A U.S. researcher who co-authored controversial papers on stem cell development will quit his post at Brigham and Womens Hospital in Boston on Sept. 1, the institution said Tuesday.

Charles Vacanti, chairman of the hospitals Department of Anesthesiology, Preoperative and Pain Medicine, was involved in the publication by a Japanese institution of two theses on so-called STAP cells whose credibility came into question earlier this year.

Vacanti, known as a mentor of Haruko Obokata at the Japanese government-affiliate Riken institute who is a key author of the papers, will remain on faculty, the Boston hospital said.

Following a one-year sabbatical Vacanti intends to focus his energies on regenerative medicine and mentoring the next generation of anesthesiologists, the hospital said.

It remains unknown if his latest step is linked with the STAP cell controversy.

According to a U.S.-based expert on regenerative medicine, Vacanti of Harvard Medical School is believed to have written an email informing his colleagues and others of his intention to resign from the post.

Paul Knoepfler, associate professor at the University of Californias Davis School of Medicine, released Vacantis email on his blog on Monday.

It is with somewhat mixed emotions that I share with you my decision to step down, it reads.

Vacanti did not mention whether his decision has to do with his involvement in the papers on STAP cells that were published in the British science journal Nature in January and retracted in July after critical errors were found.

I plan to take a one-year sabbatical to contemplate my future goals, redirect my efforts and spend time doing some of the things that I enjoy most, the email says.

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Cedars-Sinai Heart Institute Opens First-of-its-Kind Research Stem Cell Clinic for Cardiac Patients

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Newswise LOS ANGELES (Aug. 12, 2014) Regenerative medicine experts at the Cedars-Sinai Heart Institute have opened a new clinic to evaluate heart and vascular disease patients for participation in stem cell medical studies.

Led by Eduardo Marbn, MD, PhD, director of the Cedars-Sinai Heart Institute, and Timothy Henry, MD, director of the Heart Institutes Cardiology Division, the doctors and researchers at the Cedars-Sinai Heart Institute Regenerative Medicine Clinic use a scientific approach to assess the possible benefits of stem cells to repair damaged or diseased cardiovascular tissues. The clinic is believed to be the first at a major U.S. academic medical center dedicated to matching patients with appropriate stem cell clinical trials, whether those research interventions are available at the medical center or at other institutions.

The Heart Institute Regenerative Medicine Clinic offers consultative services for patients with heart and vascular disease who may qualify for investigative stem cell therapy. The goal is to provide research options to patients who remain symptomatic on their current management regimen, or for patients with stable heart disease who are concerned about disease progression.

Over the past decade, medical experts have predicted that in the future, stem cell therapies would transform heart disease treatment and save lives, said Shlomo Melmed, MD, dean of the Cedars-Sinai faculty and the Helene A. and Philip E. Hixon Distinguished Chair in Investigative Medicine. At Cedars-Sinai, we have a track record of successfully directing cardiac stem cell studies as well as transferring innovations from the laboratory to the patient bedside.

In 2009, Marbn and his team completed the worlds first procedure in which a patients own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patients heart in an effort to repair and re-grow healthy muscle in a heart that had been injured by a heart attack. Results, published in The Lancet in 2012, showed that one year after receiving the stem cell treatment, heart attack patients demonstrated a significant reduction in the size of the scar left on the heart muscle after a heart attack.

Henry has served as principal investigator of multiple large, multicenter trials in acute coronary syndromes, myocardial infarction and angiogenesis, including several ongoing cardiovascular stem cell trials. He also is principal investigator for one of seven NIH Clinical Cardiovascular Stem Cell Centers.

Our goal is to help make stem cells a regular treatment option for heart disease, Henry said. Right now, many patients with advanced heart disease have limited treatment options. Stem cells offer not only hope but a real chance of a game-changing treatment.

As part of each patients assessment in the Heart Regenerative Medicine Clinic, physicians will evaluate patients interested in participating in stem cell clinical trials at Cedars-Sinai and, for patients willing to travel at other medical institutions across the nation. For patients willing to travel to participate in research, Cedars-Sinai physicians will work closely with investigators at other centers to expedite referrals and seamlessly transfer all relevant medical records.

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Cedars-Sinai Heart Institute Opens First-of-its-Kind Research Stem Cell Clinic for Cardiac Patients

UCSD Looking For Spinal Cord Injury Patients To Test Stem Cell Treatment

The UC San Diego Health System put out a call Monday for eight spinal cord injury patients to take part in a five-year test of the safety of a new treatment involving neural stem cells.

The researchers are looking for people who suffered an injury to the middle or lower levels of the spine's thoracic vertebrae between one and two years ago. According to UCSD, the injury must be between the seventh and 12th thoracic vertebrae.

"The goal of this study is to evaluate the safety of transplanting neural stem cells into the spine for what one day could be a treatment for spinal cord injuries," said Dr. Joseph Ciacci, the study's principal investigator and a neurosurgeon at UC San Diego Health System. "The study's immediate goal, however, is to determine whether injecting these neural stem cells into the spine of patients with spinal cord injury is safe."

The doctors also want to know how long the transplanted stem cells will last, and whether drugs designed to prevent rejection by the immune system are effective, according to UCSD Health.

The researchers will also look for possible changes in motor and sensory function, bowel and bladder function, and pain levels.

The stem cells were tested in laboratory rats by Ciacci and Dr. Martin Marsala, of the UC San Diego School of Medicine. They detected signs of improved motor function with minimal side effects. The cells have also been tested for safety in human patients with amyotrophic lateral sclerosis commonly known as ALS or Lou Gehrig's Disease.

UCSD cautioned prospective test subjects that since human tests are just beginning, unforeseen risks, complications or unpredictable outcomes are possible.

The clinical trial at UC San Diego Health System is funded by Neuralstem Inc. and was launched and supported by the UC San Diego Sanford Stem Cell Clinical Center. The center was recently created to "advance leading-edge stem cell medicine and science, protect and counsel patients, and accelerate innovative stem cell research into patient diagnostics and therapy," according to UCSD.

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UCSD Looking For Spinal Cord Injury Patients To Test Stem Cell Treatment

Nationally Recognized Beverly Hills Orthopedic Surgeon, Dr. Raj, Now Offering Stem Cell Procedures to Help Patients …

Beverly Hills, California (PRWEB) August 11, 2014

Nationally recognized Beverly Hills orthopedic surgeon, Dr. Raj, is now offering stem cell procedures to help patients avoid the need for surgery. This may include joint replacement along with tendon or ligament surgery. For more information on stem cell therapy and scheduling at the Beverly Hills Orthopedic Institute, call (310) 247-0466.

As the benefit of stem cells for repair and regeneration of human tissue has evolved, the opportunity to avoid surgery has too. This includes those with cartilage degeneration, tendonitis and ligament injury. Dr. Raj has been a pioneer in bringing stem cell therapies to the forefront, and is now offering the procedures to all patients.

According to Celebrity Fitness Expert Dr. Raj, a nationally recognized Double Board Certified Orthopedic Surgeon at the Beverly Hills Orthopedic Institute, stem cell injections are being used to heal conditions that used to require surgery. Dr. Raj has been featured on The Doctors, SPIKE TV, NBC, CBS, Martha Stewart Living Radio, Beverly Hills Times and has been named Best of LA by KCAL 9 as well we making Americas Top Orthopedics List in 2007, 2009, 2010, and 2011.

Dr. Raj explains that stem cells have started a medical revolution and have altered the way doctors approach treatment. Stem cells help to regenerate the damaged cartilage within a joint and allow patients to take a more conservative route, adds Dr. Raj. Surgery should be a last case scenario after all other options have been exhausted.

For those individuals suffering from joint arthritis of the hip, knee, shoulder or ankle, surgery is an elective decision with nonsurgical options that traditionally did not alter the course of arthritis. They have merely acted as a "band aid" for pain relief, but not effective at long term relief due to healing arthritis.

Stem cell therapy offers the opportunity for relief and increased activity, while staying out of the operating room. The procedures are outpatient and safe, with minimal risks involved.

For more information on the stem cell procedures provided with the top orthopedic doctor in Los Angeles and Beverly Hills, call (310) 247-0466.

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Nationally Recognized Beverly Hills Orthopedic Surgeon, Dr. Raj, Now Offering Stem Cell Procedures to Help Patients ...

How Breast Cancer Usurps the Powers of Mammary Stem Cells

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Newswise During pregnancy, certain hormones trigger specialized mammary stem cells to create milk-producing cells essential to lactation. Scientists at the University of California, San Diego School of Medicine and Moores Cancer Center have found that mammary stem cells associated with the pregnant mammary gland are related to stem cells found in breast cancer.

Writing in the August 11, 2014 issue of Developmental Cell, David A. Cheresh, PhD, Distinguished Professor of Pathology and vice-chair for research and development, Jay Desgrosellier, PhD, assistant professor of pathology and colleagues specifically identified a key molecular pathway associated with aggressive breast cancers that is also required for mammary stem cells to promote lactation development during pregnancy.

By understanding a fundamental mechanism of mammary gland development during pregnancy, we have gained a rare insight into how aggressive breast cancer might be treated, said Cheresh. This pathway can be exploited. Certain drugs are known to disrupt this pathway and may interfere with the process of breast cancer progression.

During pregnancy, a new mammary stem cell population arises, distinct from those involved in development and maintenance of the non-pregnant gland. These stem cells remodel the breasts and lactating glands in preparation for feeding the newborn child. Normally, these stem cells contribute only to early remodeling events and are switched off by the time milk production begins.

The researchers found, however, that signals regulating stem cell activation during pregnancy appear to be hijacked by cancer cells to produce faster-growing, more aggressive tumors. This normal pathway ends up contributing to the progression of cancer, said Desgrosellier, first author of the study.

A connection between pregnancy and breast cancer has long been known. But the association between pregnancy and breast cancer risk is complex. While having a child reduces a womans risk of developing breast cancer later in life, there is also an increased short-term risk for the development of a highly aggressive form of breast cancer following each pregnancy. The current study suggests that molecules important for stem cell behavior during pregnancy may contribute to these more aggressive pregnancy-associated breast cancers, a possibility the researchers plan to investigate further.

The authors are quick to point out that their findings should not be interpreted as a reason to avoid pregnancy. The signaling pathway usurped by cancer cells is not the cause of breast cancer. Rather, they said, it may worsen or accelerate a cancer caused by other factors, such as an underlying mutation or genetic predisposition.

Our work doesnt speak to the actual cause of cancer. Rather, it explains what can happen once cancer has been initiated, said Cheresh. Heres an analogy: To get cancer, you first have to start with an oncogene, a gene that carries a mutation and has the potential to initiate cancer. Think of the oncogene as turning on a cars ignition. The signaling pathway exploited by cancer cells is like applying gas. It gets the car moving, but it means nothing if the oncogene hasnt first started the process.

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How Breast Cancer Usurps the Powers of Mammary Stem Cells

BioEden calls for transparancy and education on stem cell availability

(PRWEB UK) 11 August 2014

BioEden the specialist tooth stem cell bank calls for a more intelligent approach, transparency and public education regarding stem cell banking.

"The public needs to be made aware that the success of stem cell medicine is largely dependant on the right material being available at the right time," says Tony Veverka Group CEO of the rapidly expanding specialist bank.

"With 1 in 3 people predicted to use stem cell therapy within their lifetime people need to know what their choices are at a time when they are able to do something about it, for example obtaining stem cells from their childrens naturally shed baby teeth."

BioEden pioneered the banking of stem cells from childrens baby teeth in 2006 in Austin Texas, and now operates in 21 countries.

BioEden says its unique process has many advantages over other forms and sources of stem cells, and eliminates the costly and painful process of getting stem cells from bone marrow for example.

The BioEden process is patent protected and offers the most natural form of stem cell banking that exists today.

"It is nonsense to say that a dental surgeon needs to extract a childs baby tooth in order to get the best result. The tooth falls out naturally and providing the stem cell bank offers quality transportation and processing, not even dental intervention is required," says Mr Veverka.

There are significant advantages in banking stem cells from teeth over cord blood for example, including the potential for a much wider therapeutic application, its non-invasive, not limited to the number of cells such as with cord blood during the birthing process, and is the least expensive form of private banking there is.

Banking your child's cells is the only way of ensuring a perfect stem cell match, eliminating the emotional distress caused when no match can be found.

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BioEden calls for transparancy and education on stem cell availability