UCSF Stem Cell Research Advances with Brain Cell Mouse Transplants

Researchers at the Broad Center of Regeneration Medicine and Stem Cell Research on the Parnassus Campus of the University of California San Francisco have just published the results of two related studies involving differentiated brain cells transplanted into mice. In one case, the cells were human brain cells integrated successfully into a mouse brain; in the other, epileptic mice were cured with specialized mouse brain cells. In both studies the differentiated cells were a type of interneuron progenitor called medial ganglionic eminence (MGE) cells.  Unlike other brain stem cells that can turn into any number of specialized cells, these differentiated MGE cells have a specific function, which is to inhibit signaling in overactive nerve circuits. These experiments hold promise for future treatment of neurological disorders like Parkinson’s disease, Alzheimer’s, epilepsy, and the chronic pain and spasticity caused by spinal cord injury.

[Brain research image, courtesy of UCSF]

Drs. Arnold R. Kriegstein and Arturo Alvarez-Buylla head the neural pipeline of the UCSF stem cell center and are co-authors (with others) on the two scientific papers just published, in the May issues of Cell Stem Cell and Nature Neuroscience. In the more directly therapeutic study with epileptic mice, the team found that seizures stopped altogether in about half of the mice and were dramatically reduced in the rest. Furthermore, after only one treatment, the results were permanent. This differs markedly from other epilepsy drug treatments, which must be administered continuously and lifelong. To further test the cells' potential, the research mice were afflicted with a particularly drug-resistant form of epilepsy, which was largely cured after the injection. In an earlier cell therapy experiment at UCSF, an injection of the cultured MGE cells into a damaged mouse spinal cord significantly reduced pain.

While all of these experiments with the MGE cells demonstrated that the cells successfully integrated into the mouse brain and subsequently carried out their regulatory function, there were other benefits to the research as well. What these scientists and their colleagues learned about MGE cells' development-- namely that they require a lot of time to grow and that they correctly mimic human neural development-- makes the cells valuable for creating laboratory models of human brain diseases in which interneurons malfunction.

[Arnold Kriegstein, MD, PhD, in front of the Ray and Dagmar Dolby stem cell research building on the Parnassus Campus, courtesy of UCSF]

The lead up to this research targeting interneurons was also extremely valuable, as it required culturing the MGE cell line from more general stem cells, both embryonic and induced pluripotent. Postdoctoral researcher Cory Nichols was a key figure in the process, which required the use of key growth hormones and other molecules to shape the developmental path. Given the promise of these human MGE cells and the potential for creating the cell line in quantities adequate for use in future clinical trials, Nichols, Kriegstein, Buylla, and their co-researcher John Rubenstein have formed Neurona Therapeutics and applied for a patent, “In Vitro Production of Medial Ganglionic Eminence Precursor Cells" to commercialize their success.

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