Graft Survival Transplantation Strategies

Significant progress has been made in the transplantation protocol itself, but we have much to learn about the intrinsic potential of various donor brain tissue preparations and the in vivo cues to determine the fate of the neuroglial graft. In general, it is still believed that first trimester human fetal mesencephalic tissue is the best source for harvesting and grafting of dopaminergic neurons. This "window" can be somewhat extended (comparable numbers of surviving TH-positive grafted neurons) if cell suspensions are used instead of solid grafts. This finding was confirmed by different groups in various animal models, and most data suggest that, if survival of TH-positive cells is used as the main criterion of assessing the grafting efficacy, the younger embryonic tissues are superior to older fetal donors. Nevertheless, as discussed previously, several reports challenge this concept.

Although it may sound mostly of academic interest because all PD patients are adults, the influence of host age on graft survival merits discussion for identifying potential in vivo cues that are responsible for the integration of the implanted cells. One of the first observations made was that, in the neocortical transplants in older rats, both types of grafts, with high (early embryonic) or low (late embryonic) growth potential, survived and integrated to similar extents versus clear in vivo differences when younger host animals were used. Further studies have confirmed that migration of donor cells and integration of the grafts decrease in older hosts. On the other hand, studies analyzing host dopaminergic sprouting in the graft, in general very limited, find that it is not significantly different in young versus adult rats. Furthermore, these results were confirmed by functional studies showing that, even if the cytoarchitec-ture of the grafts in hosts of various ages may be different, the benefits are comparable. It is interesting to speculate on the clinical implications of these observations because several authors agree that the host responses are most critical to the functional benefits of fetal grafting.

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