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Clinical trials are under way using fetal cells to repair damaged neuronal circuitry. However, little is known about how transplanted immature neurons can grow anatomically correct connections in the adult central nervous system (CNS). We transplanted embryonic porcine neural cells in vivo into adult rat brains with neuronal and axonal loss typical of Parkinson's or Huntington's disease. Using complementary species-specific cellular markers, we found donor axons and CD44+ astroglial fibres in host white matter tracts up to 8 mm from CNS transplant sites, although only donor axons were capable of reaching correct gray matter target regions. This work demonstrates that adult host brain can orient growth of transplanted neurons and that there are differences in transplant donor glial and axonal growth patterns in cellular repair of the mature CNS.

Fetal striatal grafts are found to have a modular organization revealed by acetylcholinesterase (AChE) histochemistry. The AChE-rich zones represent the only portions of these grafts that are anatomically and functionally integrated into the host brain. In this study, the medial and lateral ganglionic eminences (MGEs and LGEs) were selectively dissected from the basal telencephalon of embryonic-day-14 (E14) rat fetuses to compare their relative contributions to the AChE-rich fraction of intrastriatal grafts. Separate cell suspensions prepared from either eminence were stereotaxically implanted into excitotoxically lesioned neostriatum of adult rats. Eight weeks after transplantation, grafts of the MGE were compared with those of the LGE with respect to the proportion of AChE-rich zones, graft size, graft morphology, and afferent dopaminergic innervation as revealed by tyrosine hydroxylase (TH) immunostaining. The mean AChE-rich fraction in LGE grafts (87% +/- 4%) was markedly greater than the AChE-rich fraction in MGE grafts (25% +/- 10%). The LGE grafts were also morphologically better incorporated into the lesioned host striatum, partially reconstituting the striatal morphology. There was no statistically significant difference in graft size between the two groups. The AChE-rich LGE grafts were TH immunoreactive, whereas the AChE-poor MGE grafts were not. We conclude that grafts derived exclusively from the fetal LGE reconstitute the striatal morphology and consist almost entirely of AChE-rich zones.

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