Oct 25, 2002
By rescuing damaged but nonapoptotic brain cells, transplanted neural stem cells may someday be used to treat progressive neurodegenerative diseases, according to a results of a new study in aged mice.
Dr. Evan Y. Snyder, of Harvard Medical School, and a multinational team of researchers used as a model 20-month-old mice injected with an agent to down-regulate tyrosine hydroxylase (TH) in dopaminergic neurons of the mesostriatal system without killing the neurons.
The mice then had neural stem cells implanted unilaterally above the right substantia nigra/ventral tegmental area. After 1 week, grafted cells were distributed principally on the ipsilateral side of the mesencephalon. After 3 weeks, they were found in high density on both sides of the brain, reaching as far as the hippocampus and neocortex.
Thus, it appears that neural stem cells migrate even more readily in the brains of older animals than in young adults whose brains are intact, the report indicates. Furthermore, "the majority...of [donor] cells were located not within the mesostriatal nuclei but rather surrounding the impaired dopaminergic neurons," the investigators write.
They describe their research in Nature Biotechnology published online on October 15.
The researchers also noted at three weeks, in transplanted but not sham-transplanted mice, that the number of TH+ cells had recovered nearly to values observed in intact animals.
The researchers were intrigued to find, however, that the reconstituted TH+ neurons were about 90% of host origin, "suggesting that they were 'rescued' cells." Only about a third of the grafted cells expressed markers of differentiation, mostly glia. The remainder were broadly dispersed and undifferentiated. Many of the latter cells were found to express glial-cell-line-derived neurotrophic factor.
"Our primary conclusion is that transplanted neural stem cells may possess an inherent capacity to alter the recipient host environment such that the function of imperiled and/or dysfunctional endogenous neurons is reactivated or preserved," probably by expressing trophic or neuroprotective substances or both, the authors write.
Finally, the rescue was long-lived, with TH and dopamine transporter activity persisting and the animals achieving a typical lifespan.
© 2002 Reuters Ltd