LONG-TERM SURVIVAL OF HUMAN CENTRAL-NERVOUS-SYSTEM PROGENITOR CELLS TRANSPLANTED INTO A RAT MODEL OF PARKINSONS-DISEASE

Progenitor cells were isolated from the developing human central nervo us system (CNS), induced to divide using a combination of epidermal gr owth factor and fibroblast growth factor-a, and then transplanted into the striatum of adult rats with unilateral dopaminergic lesions. Larg e grafts were found at 2 weeks survival which contained many undiffere ntiated cells, some of which were migrating into the host striatum. Ho wever, by 20 weeks survival, only a thin strip of cells remained at th e graft core while a large number of migrating astrocytes labeled with a human-specific antibody could be seen throughout the striatum. Full y differentiated graft-derived neurons, also labeled with a human-spec ific antibody, were seen close to the transplant site in some animals. A number of these neurons expressed tyrosine hydroxylase and were suf ficient to partially ameliorate lesion-induced behavioral deficits in two animals. These results show that expanded populations of human CNS progenitor cells maintained in a proliferative state in culture can m igrate and differentiate into both neurons and astrocytes following in tracerebral grafting. As such these cells may have potential for devel opment as an alternative source of tissue for neural transplantation i n degenerative diseases. (C) 1997 Academic Press.