Neuron-enriched second trimester human cultures: Growth factor response and in vivo graft survival

Grafts of first trimester fetal tissue show limited survival and integratio n in the adult CNS. Alternative grafting strategies have been sought for tr eatment of neurodegenerative disease. We have developed cultures of human s econd trimester fetal tissues to study neuronal differentiation. Grafted in to the SCID mouse striatum, aggregates of these cultures formed neuron-rich xenografts for at least 8 months. We examined the influence of various neu rotrophic factors, including basic fibroblast growth factor (bFGF), brain-d erived neurotrophic factor (BDNF), transforming growth factor-beta 1 (TGF-b eta 1), and hepatocyte growth factor (HGF), on the growth and differentiati on of neuronal and glial cell populations. BDNF promoted the survival and d ifferentiation of second trimester neurons whereas bFGF exhibited a strong proliferative effect on precursors and the astroglial population. Our data suggest that second trimester human fetal cultures contain neuroprogenitor cells that can be directed to the neuronal lineage. This process may be amp lified by treatment with BDNF, which we hypothesize could improve the long- term in vivo survival of neuron-enriched grafts.