MATURATION OF FETAL HUMAN NEURAL XENOGRAFTS IN THE ADULT-RAT BRAIN

Transplantation of human fetal neural cells has been used for several years as a treatment for Parkinson's disease. These therapeutic trials were based on a large number of rat allografts studies, and the speci es to species extrapolation appeared valid in many respects. One major difference between neurons of various species, however, is their rate of maturation; indeed, human neurons have been proven to grow much mo re slowly than rat neurons. This has been studied mostly, up to now, a t the light microscope level. In an attempt to determine the fine stru ctural correlates of this protracted development and to detail the sch edule of morphogenesis and synaptogenesis, human fetal brain stem tiss ue (at 8 weeks of gestation) was transplanted into a previously lesion ed brain area of immunosuppressed adult rats. Transplants, which were allowed to develop for 15 days to 3 months, were analyzed using the el ectron microscope. At 15 days, small cells containing a large nucleus were surrounded by wide extracellular spaces. At 1 month, grafted neur ons displayed a thin rim of cytoplasm and few thin processes. At 2 mon ths, extracellular spaces tended to diminish. Thin processes formed bu ndles and large processes extended from enlarged neurons. Major change s were observed at 3 months survival as the neuropile filled up with c ells and processes and synaptogenesis began. Comparison with a similar ultrastructural study of thalamic rat allografts shows that human cel ls develop following a pattern similar to that in rat cells but that t he duration of each maturation step is largely extended. (C) 1997 Acad emic Press.