TRANSPLANTATION OF HUMAN STRIATAL TISSUE INTO A RODENT MODEL OF HUNTINGTONS-DISEASE - PHENOTYPIC-EXPRESSION OF TRANSPLANTED NEURONS AND HOST-TO-GRAFT INNERVATION

The present study was undertaken to investigate the phenotypic express ion and integration of human striatal neurons transplanted into an ani mal model of Huntington's disease. Sprague-Dawley rats were anesthetiz ed and subjected to quinolinic acid lesions of the left striatum. Thre e human fetal cadavers were utilized for transplantation in this study (7, 8, and 10 weeks in gestation). The striatal primordia was dissect ed from each fetus and subsequently dissociated into cell suspensions. Following the initial lesion surgeries (3-4 months), the rats were re anesthetized and transplanted with human striatal cells (400,000 cells per rat). The animals were processed for histochemical analysis 9-17 weeks posttransplantation. Histochemistry was performed utilizing thio nin (Nissl staining), acetylcholinesterase, NADPH-diaphorase, and anti bodies against tyrosine hydroxylase and glial fibrillary acidic protei n. Examination of stained brain sections demonstrate that human striat al transplants grow to fill a substantial portion of the remaining str iatum, and contain clusters of immature and mature cells. Acetylcholin esterase activity is present in the transplant neuropil, varying in in tensity, and distributed in a heterogeneous fashion. In addition, host afferent dopaminergic fibers penetrate into the transplant, and are o ccasionally found in patches, NADPH-diaphorase histochemistry revealed medium sized aspiny striatal neurons of donor origin in the transplan ts. The results of this study are similar to those obtained with roden t fetal striatal transplants, and suggest that human striatal tissue i s capable of surviving, expressing normal striatal cell phenotypes, an d receiving host dopaminergic innervation.