IMPLANTATION OF XENOGENEIC TRANSGENIC NEURAL PLATE TISSUES INTO PARKINSONIAN RAT-BRAIN

Xenografting must be considered as a means of establishing neural tran splantation therapy and of securing fetal neural tissues as donor mate rial. The early stage (embryonic day 8.5, E8.5) embryonic mesencephali c neural plate (NP) from transgenic mice was examined for possible app lication in effective xenografting therapy. As recipients, Parkinsonia n rats treated with 6-hydroxydopamine were used, and as donors, GT4-2 mice into which a beta-galactosidase gene was introduced to allow brai n tissue differentiation from the recipients by X-gal staining. Three microscopic pieces of E8.5 GT4-2 mice NP were injected into the striat um of the Parkinsonian rats. Some hosts were given immunosuppressants (cyclophosphamide and FK506) (IS group), others were not (non-IS group ). Amphetamine-induced rotation was examined at days 11 and 21 after g rafting (D11 and D21, respectively), and morphological investigations were performed using hematoxylin-eosin (HE), X-gal, and thyrosine hydr oxylase (TH) staining. The rotations were counted in 30 of the 38 tran splanted rats before and after grafting. Histological data were obtain ed from 19 of these 30 rats. In 11 of them the grafts survived (surviv al group) and in the remaining 8, the grafts were unsuccessful (reject ion group). In the survival group at D11, the mean number of rotations made by transplanted rats expressed as a percentage of the number bef ore grafting (rotation percentage) decreased to 43.8% (n = 9), which, in comparison with the average of 125.9% (n = 6) in the rejection grou p, reveals significant behavioral recovery (p < 0.01). The rotation pe rcentage at D21 was 23.8% in the survival group (n = 4) and 84.5% in t he rejection group (n = 3). Behavioral recovery was thus seen to impro ve with time in the survival group. In the IS group (n = 19), the rota tion percentages averaged 74.9% (D11, n = 15) and 51.1% (D21, n = 7), while the non-IS group averages were 136.7% (D11, n = 9) and 140.7% (D 21, It = 9), indicating a tendency for better behavioral recovery in t he IS group than in the non-IS group (p < 0.05). Fifteen IS group rats were studied histologically, 10 (sacrificed on D11, D21) from the sur vival group and 5 (sacrificed on D11, D21) from the rejection group. I n the non-IS group (n = 4), there was a graft in only one rat sacrific ed on D11. There were many X-gal positive and TH positive cells in the grafts, suggesting that mouse NP survived, and differentiated into TH positive neurons in the rat brain. Xenografted NP has the potential t o cure central nervous system diseases. (C) 1997 Elsevier Science Inc.