INTRASTRIATAL GRAFTS FROM MULTIPLE DONORS DO NOT RESULT IN A PROPORTIONAL INCREASE IN SURVIVAL OF DOPAMINE NEURONS IN NONHUMAN-PRIMATES

We examined the potential for ''double grafts,'' i.e., grafts from two donors in each recipient, to enhance the total number of ventral mese ncephalic dopamine neurons that survive grafting in adult African gree n monkeys, Because dopamine cell survival in grafts represents a small percentage of the total number of neurons grafted, several human clin ical trials recently have employed grafts of tissue from multiple dono rs (e.g., from two to eight embryos per host recipient) in attempts to increase the total number of dopamine neurons that survive in grafts, Presumably, this is intended to elevate dopamine levels by providing more dopamine neurons to the damaged brain to alleviate the symptoms o f parkinsonism. While well-developed grafts with several thousand dopa mine neurons were found in most recipient animals, we observed a reduc ed total number of tyrosine hydroxylase positive neurons in the grafts in spite of the presence of some double grafts that were larger than normal, The overall growth of the grafts was impressive; some grafts w ere so large that they spanned the full dorsoventral extent of the cau date nucleus, probably reflecting the fact that twice as much tissue w as implanted in each drop site in comparison to our standard protocol, However, some animals revealed atypical patterns of neurite outgrowth that appeared limited to the grafted tissue, and at least one monkey revealed ''amorphous'' grafts generally lacking in cellular structure, which suggests a possible rejection phenomenon, These findings raise questions about the use of multiple donors and suggest that the likeli hood of rejection and/or cell death may be enhanced, which is of poten tial importance in the design of grafting strategies for clinical appl ications, (C) 1998 Elsevier Science Inc.