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 species 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 more slowly than rat neurons. This has been studied mostly, up to now, at the light microscope level. In an attempt to determine the fine structural correlates of this protracted development and to detail the schedule of morphogenesis and synaptogenesis, human fetal brain stem tissue (at 8 weeks of gestation) was transplanted into a previously lesioned brain area of immunosuppressed adult rats. Transplants, which were allowed to develop for 15 days to 3 months, were analyzed using the electron microscope. At 15 days, small cells containing a large nucleus were surrounded by wide extracellular spaces. At 1 month, grafted neurons displayed a thin rim of cytoplasm and few thin processes. At 2 months, extracellular spaces tended to diminish. Thin processes formed bundles and large processes extended from enlarged neurons. Major changes were observed at 3 months survival as the neuropile filled up with cells and processes and synaptogenesis began. Comparison with a similar ultrastructural study of thalamic rat allografts shows that human cells develop following a pattern similar to that in rat cells but that the duration of each maturation step is largely extended. (C) 1997 Academic Press.