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 Parkinson’s 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.
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-centimetre radius along the track, a volume bigger than an entire mouse brain.
Several researchers hope to use Lim’s 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.
A team of scientists from UCSF and StemCells, a biotechnology company based in Newark, California, wants to use the device to treat Pelizaeus–Merzbacher disease, a deadly neurodegenerative disorder. Last year, the company reported promising results from a phase I clinical trial testing neural stem-cell transplants for treating this disease.
Track to improvement
Lim's device could cut down on the number of injections required for cell treatments, says Zeng. It could give more precise control of the volume of cells delivered and ensure that the cells delivered into the brain stay in the brain, avoiding the problem of reflux, in which cells injected using straight needles flow back out to the brain surface along the needle’s path.
“Every time you put a needle into the brain, you run the risk of a hemorrhage and raise the risk of unwanted effects,” says Ian Duncan, a neuroscientist at the University of Wisconsin–Madison, who is not involved in Lim’s project.
Also, unlike other needles used for cell therapies, Lim’s device contains no ferromagnetic metals and so is compatible with MRI. The imaging would enable researchers to monitor patients for signs of hemorrhaging and to combine cell therapy with other techniques, such as depositing electrodes for deep brain stimulation, an experimental therapy for Parkinson's disease.