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Dziewczapolski, G.* ; Lie, D.C.* ; Ray, J.* ; Gage, F.H.* ; Shults, C.W.*

Survival and differentiation of adult rat-derived neural progenitor cells transplanted to the striatum of hemiparkinsonian rats.

Exp. Neurol. 183, 653-664 (2003)

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We investigated the survival, distribution and differentiation capabilities of adult rat hippocampus-derived progenitor cells (AHPs) by grafting them into either the intact or dopamine (DA)-denervated adult rat striatum (ST). Furthermore, we tested the effects of the in vivo administration of retinoic acid (RA) on the differentiation of the grafted cells. AHPs, prelabeled in vitro with bromodeoxyuridine (BrdU) and primed with RA, were transplanted bilaterally into the ST of hemiparkinsonian rats. Twenty animals were divided in four groups: three groups received i.p. injections of RA (1.5 mg/kg/day) for 1, 2 or 4 weeks and one group received vehicle injections for 4 weeks. Approximately 60% of the implanted BrdU-immunoreactive (BrdU+) cells were present in either intact or lesioned ST after 5 weeks of transplantation, with a striking widespread radial distribution from the implantation site. The cells became morphologically integrated with the surrounding host tissue, with no evidence of tumor formation. Approximately 18% of the BrdU+ cells were immunoreactive for the glial precursor marker NG2 and occasionally BrdU+ cells co-expressed the neuronal marker TuJ1. This differentiation pattern was similar in the intact and DA-denervated ST. Although further research is needed to find more adequate methods to drive the differentiation of these cells toward the desired phenotypes, the survival, differentiation potential and widespread distribution throughout the ST observed in this study suggest that AHPs may be useful in treatment of degenerative disorders affecting the nervous system.

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