Intrastriatal and intranigral grafting of hNT neurons in the 6-OHDA rat model of Parkinson's disease

The clinical findings on neural transplantation for Parkinson's disease (PD ) reported thus far are promising but many issues must be addressed before neural transplantation can be considered a routine therapeutic option for P D. The future of neural transplantation for the treatment of neurological d isorders may rest in the discovery of a suitable alternative cell type for fetal tissue. One such alternative may be neurons derived from a human tera tocarcinoma (hNT). hNT neurons have been shown to survive and integrate wit hin the host brain following transplantation and provide functional recover y in animal models of stroke and Huntington's disease. In this study, we de scribe the transplantation of hNT neurons in the substantia nigra (SN) and striatum of the rat model for PD, Twenty-seven rats were grafted with one o f three hNT neuronal products; hNT neurons, hNT-DA neurons, or lithium chlo ride (LiCl) pretreated hNT-DA neurons. Robust hNT grafts could be seen with anti-neural cell adhesion molecule and anti-neuron-specific enolase immuno staining. Immunostaining for tyrosine hydroxylase (TH) expression revealed no TH-immunoreactive (THir) neurons in any animals with hNT neuronal grafts . THir cells were observed in 43% of animals with hNT-DA neuronal grafts an d all animals with LiCl pretreated hNT-DA neuronal grafts (100%). The numbe r of THir neurons in these animals was low and not sufficient to produce si gnificant functional recovery. In summary, this study has demonstrated that hNT neurons survive transplantation and express TH in the striatum and SN, Although hNT neurons are promising as an alternative to fetal tissue and m ay have potential clinical applications in the future, further improvements in enhancing TH expression are needed. (C) 2000 Academic Press.