The effect of prior in vitro exposure of donor cells to trophic factors in neurotransplantation

The ability of PC12 cells to regenerate processes is substantially enhanced in vitro if they have been previously exposed to nerve growth factor (NGF-primed), compared to cells that have not been exposed (NGF-naive). These studies were carried out to determine if the enhanced neuritogenic ability of NGF-primed cells is retained following transplantation. NGF-naive or NGF-primed PC12 cells were transplanted into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and allowed to survive for 2 weeks. Mice were given daily injections of cyclosporin A (CyA) to prevent anti-species graft rejection. The transplanted PC12 cells were visualized by tyrosine hydroxylase immunoreactivity. The NGF-naive transplanted cells formed dense clusters and large tumor masses in more than half the animals. Only a few of the naive PC12 cells had short processes. In contrast, many of the transplanted NGF-primed PC12 cells had processes. Furthermore, fewer of the animals transplanted with primed cells produced tumor masses in the striatum compared to animals that received NGF-naive cells. Transplantation of NGF-naive PC12 cells leads to a significant increase in the number of dopaminergic neurons in the host substantia nigra (SN) compared to MPTP-treated animals. The increase of host dopaminergic neurons was not statistically significant when NGF-primed PC12 cells were used. Following MPTP treatment and PC12 cell transplantation, injection of CyA did not affect the dopaminergic neurons in the host SN. These data suggest that exposure of cells to trophic factors, prior to transplantation, can enhance their level of differentiation and integration into the host brain. (C) 1996 Academic Press, Inc.