Xenografting of fetal pig ventral mesencephalon corrects motor asymmetry in the rat model of Parkinson's disease

Abstract

A suspension of cells from embryonic day 21 fetal pig ventral mesencephalon was transplanted into the striatum of 20 immunosuppressed rats with 6-hydroxydopamine-induced lesions of the nigrostriatal dopamine pathway. Of these rats, 15 showed reduction of amphetamine-induced ipsilateral rotation by 9 weeks and complete reversal of rotation by 14-17 weeks. Animals maintained stable reversal of rotations (contralateral direction) until cessation of Cyclosporin A (CyA) treatment at 15-20 weeks. Within 4-9 weeks after CyA removal, these rats showed exclusively ipsilateral rotations during behavioral testing which were comparable to pre-transplant levels, suggesting that the grafts were rejected upon cessation of CyA treatment. Rats were sacrificed and tyrosine hydroxylase (TH) immunohistochemistry was performed at several time points, both on and off CyA, to examine a possible correlation between the degree of rotational behavior and the number of TH-positive surviving grafted cells. Staining showed large numbers (230-12,329) of TH-positive surviving cells in animals displaying a high degree of rotational correction (1.6 to -9.6 net ipsilateral rotations/min) after cessation of CyA treatment. Two control groups, those transplanted with non-neuronal cells from the pig ventral mesencephalon (n = 5) and those receiving only daily CyA injections (n = 4) showed no significant reduction of net ipsilateral rotations throughout the experiment. No TH-positive surviving cells were seen in the one non-neuronal transplant analyzed. This data demonstrates long-term retention of xenografted tissue with immunosuppression and its concomitant restoration of normal motor behavior in the rat model of Parkinson's disease.

Neural stem/progenitor cells as a promising candidate for regenerative therapy of the central nervous system

“…In fact, porcine fetal cells have been proven to be an efficient source for cell therapy in animal models of neurodegenerative diseases. Interest in these cells started to grow after first studies revealed that xenografts derived from the ventral mesencephalon of pigs (21–26 days of gestation) could survive in the brain of a rat model of Parkinson disease under immunosuppression (Freeman et al, 1988; Huffaker et al, 1989). Beyond the long-term survival, xenotransplanted neural cells also displayed a long-distance axonal outgrowth (Wictorin et al, 1990; Deacon et al, 1994).…”

The immunological challenges of cell transplantation for the treatment of Parkinson's disease

“…To avoid the ethical issues of using human FVM tissue, studies have examined the use of porcine FVM tissue as an alternative transplant [50-59]. In contrast to the human FVM tissue, porcine tissue is relatively easy to obtain and harvest can be timed accordingly to transplant days.…”

The Use of Xenotransplantation in Neurodegenerative Diseases: A Way to Go?

“…In 1989, Huffaker and colleagues demonstrated porcine neuroblasts, derived from pig foetal ventral mesencephalum at 21 days of gestation, were able to survive 15-20 weeks in a rat model of Parkinson's disease, albeit with supplements of the immunosuppressant, cyclosporine A (Huffaker et al, 1989). Immunological analysis of the transplanted tissue revealed the presence of tyrosine hydroxylase (TH) positive dopaminergic neurons in grafted striatum.…”