Category Archives: Stem Cells

The Hope and Promise of Stem Cells | Len Zon | TEDxLongwood
This talk was given at a local TEDx event, produced independently of the TED Conferences. Imagine being able to reprogram the cells from a piece of skin and transform them into cells that can...

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The Hope and Promise of Stem Cells | Len Zon | TEDxLongwood - Video

Clive Randell, 57, injured his leg in a motorcycle accident in 2011 Thanks to a new stem cell procedure, he can now ride his bike again Stem cells taken from the pelvis are blended with gel to 'glue' the bone

By David Gerrie

Published: 16:01 EST, 12 July 2014 | Updated: 19:59 EST, 12 July 2014

A pioneering stem cell procedure to repair fractured bones could provide a lifeline for accident victims facing the amputation of a limb.

The development involves harvesting stem cells master cells that are able to transform into any kind of body tissue from the patients pelvis, blending them with a specially created gel and injecting the solution into the damaged bone.

One patient already benefiting is lifelong motorcycle enthusiast Clive Randell who suffered horrific injuries to his left leg when his Harley-Davidson was rammed by a car in 2011.

On yer bike: Clive Randell, 57, pictured with his 'saviour' Professor Anan Shetty at Kents Canterbury Christ Church University, can now ride his bike again after undergoing the new stem cell procedure

He suffered multiple open fractures, leaving bone protruding through the skin, and extensive skin loss. Doctors repeatedly told him his leg would have to be amputated.

Today, though, Clive, 57, is back on his feet and, astonishingly, also his bike thanks to the ground-breaking stem-cell treatment.

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Saved from amputation - how a stem cell gel rebuilt my shattered leg

STORY HIGHLIGHTS

For more, watch "Sanjay Gupta | M.D." on Saturday at 4:30 p.m. and Sunday at 7:30 a.m. ET.

(CNN) -- In medical school, Gerald Karpman was taught that when it comes to matters of the heart, what's done is done.

"If you survived the heart attack, you survived at the level that you were going to be," he recalls. "Whatever damage was done was permanent."

That thinking has prevailed until very recently, when studies involving a handful of patients showed an infusion of stem cells might help rebuild healthy hearts in heart attack survivors.

On March 7, Karpman joined that perilous club. A dermatologist in Camarillo, California, and a former marathon runner, the 66-year-old had a rigorous routine: eight to 10 miles of walking each day and a meticulous, meatless diet.

But that morning, sitting at his home computer, a pain kicked in.

"Within about 30 seconds, I was in extreme discomfort," recalls Karpman, who says it was worse than the kidney stones he once suffered. "I couldn't sit still. I mean even driving the car (to the hospital), I couldn't put a seat belt on; I'm just moving around, just trying to think of something else."

Karpman made it to Los Robles Hospital and Medical Center in Thousand Oaks, where doctors used stents to reopen an artery in his heart and save his life.

As he lay recovering, he took in some grim news: Nearly 20% of his heart muscle was dead, starved of oxygen. Dead heart tissue leaves a scar, interrupting the coordinated muscle action that makes the heart such an efficient pump.

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Heart attack damage may be reversible

PUBLIC RELEASE DATE:

10-Jul-2014

Contact: Lucky Tran lt2549@cumc.columbia.edu 212-305-3689 Columbia University Medical Center

NEW YORK, NY (July 10, 2014) Columbia University Medical Center (CUMC) researchers have created a way to develop personalized gene therapies for patients with retinitis pigmentosa (RP), a leading cause of vision loss. The approach, the first of its kind, takes advantage of induced pluripotent stem (iPS) cell technology to transform skin cells into retinal cells, which are then used as a patient-specific model for disease study and preclinical testing.

Using this approach, researchers led by Stephen H. Tsang, MD, PhD, showed that a form of RP caused by mutations to the gene MFRP (membrane frizzled-related protein) disrupts the protein that gives retinal cells their structural integrity. They also showed that the effects of these mutations can be reversed with gene therapy. The approach could potentially be used to create personalized therapies for other forms of RP, as well as other genetic diseases. The paper was published recently in the online edition of Molecular Therapy, the official journal of the American Society for Gene & Cell Therapy.

"The use of patient-specific cell lines for testing the efficacy of gene therapy to precisely correct a patient's genetic deficiency provides yet another tool for advancing the field of personalized medicine," said Dr. Tsang, the Laszlo Z. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology.

While RP can begin during infancy, the first symptoms typically emerge in early adulthood, starting with night blindness. As the disease progresses, affected individuals lose peripheral vision. In later stages, RP destroys photoreceptors in the macula, which is responsible for fine central vision. RP is estimated to affect at least 75,000 people in the United States and 1.5 million worldwide.

More than 60 different genes have been linked to RP, making it difficult to develop models to study the disease. Animal models, though useful, have significant limitations because of interspecies differences. Researchers also use human retinal cells from eye banks to study RP. As these cells reflect the end stage of the disease process, however, they reveal little about how the disease develops. There are no human tissue culture models of RP, as it would dangerous to harvest retinal cells from patients. Finally, human embryonic stem cells could be useful in RP research, but they are fraught with ethical, legal, and technical issues.

The use of iPS technology offers a way around these limitations and concerns. Researchers can induce the patient's own skin cells to revert to a more basic, embryonic stem celllike state. Such cells are "pluripotent," meaning that they can be transformed into specialized cells of various types.

In the current study, the CUMC team used iPS technology to transform skin cells taken from two RP patientseach with a different MFRP mutationinto retinal cells, creating patient-specific models for studying the disease and testing potential therapies.

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Patient-specific stem cells and personalized gene therapy

The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise-the hope of fixing disease-causing genes in humans, for example-as well as questions and safety concerns.

Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells-either for research purposes or to fix a genetic mutation for therapeutic purposes-they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one.

Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world.

He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes-such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro-including gene editing-might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease.

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No extra mutations in modified stem cells

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Newswise LA JOLLA-The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise--the hope of fixing disease-causing genes in humans, for example--as well as questions and safety concerns. Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells--either for research purposes or to fix a genetic mutation for therapeutic purposes--they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one. Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world. He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes--such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro--including gene editing--might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease. They edited the genes of some cells using one of two HDAdV designs, edited others using one of two TALEN proteins, and kept the rest of the cells in culture without editing them. Then, they fully sequenced the entire genome of each cell from the four edits and control experiment.

While all of the cells gained a low level of random gene mutations during the experiments, the cells that had undergone gene-editing--whether through HDAdV- or TALEN-based approaches--had no more mutations than the cells kept in culture.

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No Extra Mutations in Modified Stem Cells, Study Finds

By Marcus Johnson

Researchers at Brown University have found that adipose-derived human stem cells (ASCs) might be highly resistant to methotrexate (MTX), a common chemotherapy drug. ASCs can ultimately become bone and other vital tissues throughout the body, which could be key for researchers looking to protect bone tissue from the damage caused by MTX treatment. MTX, which is used to treat a number of different cancers including acute lymphoblastic leukemia, causes the loss of bone density and has an adverse effect on bone marrow derived stem cells.

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 wouldnt have these issues.

Beane examined how MTX affects stem cells and certain tissues in the body and said that the resistance of certain stem cells to the drugs toxicity could mean new possibilities in the drug development realm. The researchers are now looking to find a way to make their study practical for doctors that are treating patients suffering from cancer. The next step is to test ASC survival in animal trials, where researchers will determine how the cells fare in mice that are also hit with the chemotherapy drug.

The study was published in the journal, Experimental Cell Research.

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Brown University Researchers Discover Chemo Resistant Stem Cells

Last week, the scientific journal Nature retracted two papers which claimed that skin cells could be turned into stem cells. PBS NewsHour interviewed lead author Dr. Charles Vacanti of Brigham and Womens Hospital about the studies in January.

Vacanti and scientists from the RIKEN Institute in Japan claimed that bathing adult mouse cells in a mild acid made the cells behave like embryonic stem cells. It appeared to be an inexpensive way to create stem cells without destroying an embryo.

Controversy surrounding embryonic stem cells has slowed research progress. While it is possible to make stem cells from other sources, doing so is costly and takes time. If true, the finding would have opened new avenues for stem cell-related research and therapies.

But other scientists could not recreate stimulus-triggered acquisition of pluripotency (STAP) cells. An investigation in April found that RIKEN Institute junior scientist Haruko Obokata had falsely identified some of the images in the study, and plagiarized some of the descriptions in the paper. The studies authors pointed to five more errors when the journal printed its retraction last week, including images that claimed to show two different things, but actually showed the same thing.

We apologize for the mistakes included in the Article and Letter, the authors wrote in a statement. These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC phenomenon is real.

Original post:
Scientific journal Nature retracts controversial stem cell papers

PUBLIC RELEASE DATE:

7-Jul-2014

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research

Researchers at the University of Birmingham, UK, led by Dr. Ben Scheven, Dr. Wendy Leadbeater and Ben Mead have discovered that stem cells isolated from the teeth, termed dental pulp stem cells (DPSC), can protect retinal ganglion cells (RGCs) from death following injury and promote regeneration of their axons along the optic nerve.

RGC loss is the leading cause of blindness and can arise through traumatic injury or degenerative diseases such as glaucoma. Neurotrophic factors (NTFs), which travel along the axon of a neuron to a cell body act as survival signals however, following injury or disease, this supply is lost and RGCs die. Supplementation of injured RGC with an alternative source of NTFs is paramount to protecting them from death.

The study, reported on Neural Regeneration Research (Vol. 9, No. 6, 2014), confirmed that DPSCs naturally express multiple NTFs which can supplement the lost supply of NTF and protect RGCs from death as well as promote regeneration of their axons. "Cell therapy is a promising treatment option as it provides a potentially limitless source of multiple growth factors for injured neurons", stressed first author Ben Mead. He also said "For clinical application, comparisons with other stem cells as well as development of safe delivery mechanisms are to be investigated in the future".

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Article: "Dental pulp stem cells, a paracrine-mediated therapy for the retina" by Ben Mead1, 2, Ann Logan1, Martin Berry1, Wendy Leadbeater1, Ben A. Scheven2

(1 Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, United Kingdom; 2 School of Dentistry, University of Birmingham, Birmingham B4 6NN, United Kingdom)

Mead B, Logan A, Berry M, Leadbeater W, Scheven BA. Dental pulp stem cells, a paracrine-mediated therapy for the retina. Neural Regen Res. 2014;9(6):577-578.

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Dental pulp stem cells promote the survival and regeneration of retinal cells after injury

Scientists have developed a new technique to regrow human corneas.

Using key tracer molecules, researchers have been able to hunt down elusive cells in the eye capable of regeneration and repair.

They transplanted these regenerative stem cells into mice creating fully functioning corneas.

Writing in the journal Nature, they say this method may one day help restore the sight of victims of burns and chemical injuries.

Limbal stem cells are crucial for healthy eyesight these cells work to maintain, repair and completely renew our corneas every few weeks.

Without them the cornea the transparent outermost layer of the eye would become cloudy and our vision disrupted.

A deficiency of these cells due to disease or damage through injury to the eye is among the commonest reasons behind blindness worldwide.

But the cells have so far been extremely difficult to identify, buried in a matrix of other structures in the limbal part of the eye the junction between the cornea and the white of the eye (the sclera).

Now scientists from the Massachusetts Eye and Ear Infirmary, Boston Childrens Hospital, Brigham and Womens Hospital and the VA Boston Healthcare System have identified a key tracer molecule known as ABCB5 naturally present on the surface of limbal stem cells.

Though ABCB5 has been known about for some time in other parts of the body, this is the first time it has been spotted on LSCs, helping to single out these elusive cells.

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Scientists use stem cells to regenerate human corneas