The idea of treating developmental and neurodegenerative disorders by growing new brain cells has taken a major step forward, according to results of two studies appearing in the November issue of Nature Biotechnology. Evan Snyder and colleagues at Harvard Medical School have shown that neural progenitor cells, harvested from human fetal brain tissue, are capable of repeated regeneration (in vitro) and can propagate into all types of nerve cells by epigenetic (basic fibroblast growth factor) or genetic (constitutively downregulated v-myc) means. They went on to show that, in cell cultures, these cells can compensate for the enzyme deficiency that causes Tay-Sachs disease, and that in living mice, the cells grow, migrate and differentiate into the appropriate types of cells when injected into different brain regions. What's more, in a mouse with a genetic defect that results in a failure of granule cells to develop in the cerebellum, the human stem cells replaced the missing cells.
In a parallel study, Ron McKay, Oliver Brüstle and colleagues injected human neural stem cells into the cerebral ventricles of rat embryoes. In the weeks following the transplant, the cells were found to have grown and migrated to multiple regions of the rats' brains, where they differentiated appropriately into all three major cell types. The transplanted cells were able to replace large areas of the subventricular zone. Many of the human cells occupying the white matter develop an oligodendroglial phenotype and participate in myelination of host axons, making this a potentially very interesting model for studying the mechanism of myelin repair in demyelinating diseases. Stringent tests of safety and efficacy are still needed before we will know whether neural stem cells could in fact be used to treat humanm brain disorders, but the new findings would seem to add luster to this dream.—June Kinoshita
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- Flax JD, Aurora S, Yang C, Simonin C, Wills AM, Billinghurst LL, Jendoubi M, Sidman RL, Wolfe JH, Kim SU, Snyder EY. Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat Biotechnol. 1998 Nov;16(11):1033-9. PubMed.
- Brüstle O, Choudhary K, Karram K, Hüttner A, Murray K, Dubois-Dalcq M, McKay RD. Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats. Nat Biotechnol. 1998 Nov;16(11):1040-4. PubMed.