LONG-TERM DELAYED VASCULARIZATION OF HUMAN NEURAL TRANSPLANTS TO THE RAT-BRAIN

Human neural transplants are being developed to treat Parkinson's dise ase. Previous characterization of human transplants focused on neurona l development, while little is known of the interaction between the tr ansplant and its environment, among which blood is of prime importance . We evaluated here the formation of blood vessels in human neural xen ografts placed into the brain of rats immunosuppressed with cyclospori n A. Using capillary wall markers, we found that human transplants rem ain virtually nonvascularized for more than 1 month. Angiogenesis take s place very slowly and the density of blood vessels is still quite po or after 3 months, the fine structure of these capillaries, when they form, is apparently normal. Functional studies indicate that the vascu lar network formed in the transplant allows blood circulation and exhi bits a working barrier to macromolecules. Glucose uptake and consumpti on and cytochrome oxidase activity are almost undetectable up to 3 mon ths after grafting. These results demonstrate that vascularization is much delayed in human xenografts into the rat brain. This delay is lik ely to be dependent on the maturation of the transplanted tissue. A de differentiation of human endothelial cells cotransplanted with neural cells occurs since histochemical and immunocytochemical markers reveal ing endothelial cells in the human fetus are not present up to 1 month in the transplant. The origin of this phenomenon is a matter of specu lation. How neural cells survive and mature in such conditions are iss ues of prime interest for the future of human neural grafting.