MICROGLIAL CHIMERISM IN HUMAN XENOGRAFTS TO THE RAT-BRAIN

Neural tissue from human fetuses is currently used for intracerebral transplantation to treat patients with Parkinson's disease. The development of the human fetal tissue following grafting has been considered mostly, up to now, from the neuronal point of view in xenografts. Very little is known, in contrast, about non-neuronal, glial, or vascular cells in the grafts. Comparison of the data gathered on the development of grafted human neurons with those obtained in comparable studies using rat transplants has demonstrated species-specific features. We have therefore undertaken a series of studies dealing with nonneuronal cells in human-to-rat transplants to reveal other possible species-specificity of the human tissue. This study has, ac; cordingly, been devoted to the immunohistochemical analysis of microglia of host and donor origins in a human to rat xenograft paradigm allowing clear distinction of the origin of the cells. Human neural tissue was transplanted as a cell suspension into the thalamus of adult rats. Amoeboid human microglia were observed in 1-, 2-, and 3-month-old transplants, but their density, already relatively low at the first stage, decreased further over time. Ramified human microglia were only occasional. In sharp contrast, host rat microglia rapidly invaded the transplant in the absence of any sign of necrosis. The rat cells exhibited first an amoeboid morphology but progressed at the later stages toward a more mature, ramified morphology. These results indicate that donor microglia are quite few in number at first and, at least, do not proliferate actively after transplantation. They seem rather to disappear over time. The parallel migration of a large number of host microglia into the transplant and the apparent maturation of these cells lead to the formation of a cellular chimaera. Extrapolation of these results to clinical neural grafting suggests that most, a not all, microglia in fetal transplants may rapidly be of host origin in patients.