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.

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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.

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Genetically corrected stem cells spark muscle regeneration