Category Archives: Stem Cells

The flexible needles could help doctors deliver stem cells to broader areas of the brain with fewer injections. Such therapies are being investigated for Parkinson's disease, stroke and other neurodegenerative disorders

By Monya Baker and Nature magazine

The injection system can bend sideways, delivering therapeutic stem cells to the brain through fewer holes in the skull. Image: Flickr/TschiAe

As the surgical team prepared its instruments, a severed human head lay on the plastic tray, its face covered by a blue cloth. It had thawed over the past 24 hours, and a pinky-sized burr hole had been cut near the top of its skull. Scalp covered with salt-and-pepper stubble wrinkled above and below a pink strip of smooth bone.

Over the next two hours, the head would be scanned in a magnetic resonance imaging (MRI) machine as the researchers, led by Daniel Lim, a neurosurgeon and stem-cell scientist at the University of California, San Francisco, tested a flexible needle for delivering cells to the brain.

Several laboratories are investigating ways to treat neurological diseases by injecting cells into patients brains, and clinical trials are being conducted for Parkinsons disease, stroke and other neurodegenerative diseases. These studies follow experiments showing dramatic improvements in rats and mice. But as work on potentially therapeutic cells has surged ahead, necessary surgical techniques have lagged behind, says Lim.

In 2008 researchers led by Steven Goldman at the University of Rochester in New York showed that they could make severely disabled mice able to walk by injecting human glial progenitor cells into five sites in the rodents' brains.

Those results are encouraging, but a human brain is more than 1,000 times larger than a mouse brain, and delivering cells to the right places is much harder. People know how to get cells into animals but forget about the scale-up problem with humans, Lim says.

Necessary tools Working with bioengineers and neurosurgeons, Lim designed a needle that bends. First, a straight, thin tube is injected into the brain and a flexible nylon catheter pushed through it. A deflector inside the tube arcs the catheter up and away from the entry track, and an even narrower plunger ejects cells from the catheter. In one injection, the device can deposit cells anywhere within a 2-centimeter radius along the track, a volume bigger than an entire mouse brain.

Several researchers hope to use Lims device for clinical trials in brain cancer and neurodegenerative disease. Xianmin Zeng, a stem-cell scientist at the Buck Institute in Novato, California, who worked with Lim to test the device on swine, says she hopes to file an application to use the device in clinical trials for Parkinson's before the end of 2014.

More:
Bendable Needles Developed to Deliver Stem Cells into Brains

Mar. 5, 2013 Researchers at the University of Minnesota's Lillehei Heart Institute have combined genetic repair with cellular reprogramming to generate stem cells capable of muscle regeneration in a mouse model for Duchenne Muscular Dystrophy (DMD).

The research, which provides proof-of-principle for the feasibility of combining induced pluripotent stem cell technology and genetic correction to treat muscular dystrophy, could present a major step forward in autologous cell-based therapies for DMD and similar conditions and should pave the way for testing the approach in reprogrammed human pluripotent cells from muscular dystrophy patients.

The research is published in Nature Communications.

To achieve a meaningful, effective muscular dystrophy therapy in the mouse model, University of Minnesota researchers combined three groundbreaking technologies.

First, researchers reprogrammed skin cells into "pluripotent" cells -- cells capable of differentiation into any of the mature cell types within an organism. The researchers generated pluripotent cells from the skin of mice that carry mutations in the dystrophin and utrophin genes, causing the mice to develop a severe case of muscular dystrophy, much like the type seen in human DMD patients. This provided a platform that would mimic what would theoretically occur in human models.

The second technology employed is a genetic correction tool developed at the University of Minnesota: the Sleeping Beauty Transposon, a piece of DNA that can jump into the human genome, carrying useful genes with it. Lillehei Heart Institute researchers used Sleeping Beauty to deliver a gene called "micro-utrophin" to the pluripotent cells they were attempting to differentiate.

Much like dystrophin, human micro-utrophin can support muscle fiber strength and prevent muscle fiber injury throughout the body. But one key difference between the two is in how each is perceived by the immune system. Because dystrophin is absent in muscular dystrophy patients, its presence can prompt a devastating immune system response. But in those same patients, utrophin is active and functional, making it essentially "invisible" to the immune system. This invisibility allows the micro-utrophin to replace the dystrophin and progress the process of building and repairing muscle fiber within the body.

The third technology utilized is a method to produce skeletal muscle stem cells from pluripotent cells -- a process developed in the laboratory of Rita Perlingeiro, Ph.D., the principal investigator of the latest study.

Perlingeiro's technology involves giving pluripotent cells a short pulse of a muscle stem cell protein called Pax3. The Pax3 protein pushes the pluripotent cells to become muscle stem cells, and allows them to be expanded exponentially in number. The Pax3-induced muscle stem cells were then transplanted back into the same strain of muscular dystrophy mice from which the pluripotent stem cells were originally derived.

Combined, the platforms created muscle-generating stem cells that would not be rejected by the body's immune system. According to Perlingeiro, the transplanted cells performed well in the dystrophic mice, generating functional muscle and responding to muscle fiber injury.

Continued here:
Genetically corrected stem cells spark muscle regeneration

Newswise HOUSTON -- (March 1, 2013) -- The removal of a genetic roadblock could improve the efficiency of converting adult cells into stem cells by 10 to 30 times, report scientists from The Methodist Hospital Research Institute and two other institutions in the latest issue of Cell.

"The discovery six years ago that scientists can convert adult cells into inducible pluripotent stem cells, or iPSCs, bolstered the dream that a patient's own cells might be reprogrammed to make patient-specific iPSCs for regenerative medicine, modeling human diseases in petri dishes, and drug screening," said Rongfu Wang, Ph.D., Principal Investigator and Director of the Center for Inflammation and Epigenetics. "But reprogramming efficiency has remained very low, impeding its applications in the clinic."

Wang and his group identified a protein encoded by the gene Jmjd3 (also called KDM6B) as a roadblock in the stem cell conversion process. Jmjd3 is known to be involved in many biological processes, including the maturation of nerve cells and immune cell differentiation.

Wang and his team are the first to identify Jmjd3's role in inhibiting the reprogramming process. They found knockdown or deletion of Jmjd3 in young mouse fibroblasts was enough to greatly enhance reprogramming efficiency.

Our findings demonstrate a previously unrecognized role of Jmjd3 in cellular reprogramming and provide molecular insight into the mechanisms by which the Jmjd3-PHF20 axis controls this process," said Helen (Yicheng) Wang, co-principal investigator.

In investigating Jmjd3 and its role in iPSC reprogramming, Wang's team found Jmjd3 has two previously unknown functions -- it helps regulate cell growth and cellular aging and Jmjd3 deactivates another nuclear protein, PHF20. The scientists learned during the study that PHF20 is required for cellular reprogramming, because cells without PHF20 failed to generate iPSCs.

"So when it comes to increasing iPSC yields, knocking down Jmjd3 is like hitting two birds with one stone," Rongfu Wang said.

Jmjd3 may not be the only genetic roadblock to stem cell conversion.

"Removal of multiple roadblocks could further enhance the reprogramming efficiency with which researchers can efficiently generate patient-specific iPSCs for clinical applications," Wang said.

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Originally posted here:
Reprogramming Adult Cells to Stem Cells Works Better with One Gene Turned Off

Bone Marrow aspirated stem cells injected into the shoulder

By: Marc Darrow

See the article here:
Bone Marrow aspirated stem cells injected into the shoulder - Video

by JEAN ENERSEN / KING 5 News

KING5.com

Posted on February 27, 2013 at 10:36 PM

As Baby Boomers age, the number of joint replacements is going up. But even those from Generation X are now wearing out their joints, and replacements dont last forever. Paul Lyon of Gig Harbor went to Colorado looking for a better solution. Lyon says even climbing the stairs was difficult for him, but he didnt want to get a knee replacement. So instead of surgery last September, he headed to a clinic near Denver that specializes in stem cell repair.

The Regenexx procedure allows you to take your cells and try to heal your body. Dr. Christopher Centeno pioneered this less-invasive procedure eight years ago. Stem cells are harvested from a patients hip. We take those cells, we concentrate them in much, much higher numbers, and then, we place them very precisely in the spot in need of repair, Centeno said. The clinic also treats athletes, some as young as 16, with orthopedic injuries. It fits patients like Paul, in their 40s to 80s with joint damage, who still want to push the limits. Lyon plans to get his second knee treated, but not until after ski season. He paid $7,000 for his procedure, which isnt covered by insurance. But he says his money was well spent. I've had friends who've had replacements, with great success, extremely painful, but they're still limited on what they can do so, he said. I'm hoping to be able to ski for a long time with the stem cells. Maybe I'll have to cut back on the level of skiing I'm doing, but I think I'll be OK. When Lyon skies, he hikes five hours up Crystal Mountain, then skies down. He says he couldnt have done this a year ago.

The procedure doesnt come without controversy. Its still considered experimental and doesnt work for every patient.

Related links:

Regenexx website

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Stem cells used to repair knees, joint damage