MICROGLIAL CHIMERISM IN HUMAN XENOGRAFTS TO THE RAT-BRAIN

Neural tissue from human fetuses is currently used for intracerebral t ransplantation to treat patients with Parkinson's disease. The develop ment 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 developmen t of grafted human neurons with those obtained in comparable studies u sing rat transplants has demonstrated species-specific features. We ha ve therefore undertaken a series of studies dealing with nonneuronal c ells in human-to-rat transplants to reveal other possible species-spec ificity of the human tissue. This study has, ac; cordingly, been devot ed to the immunohistochemical analysis of microglia of host and donor origins in a human to rat xenograft paradigm allowing clear distinctio n of the origin of the cells. Human neural tissue was transplanted as a cell suspension into the thalamus of adult rats. Amoeboid human micr oglia 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 con trast, host rat microglia rapidly invaded the transplant in the absenc e of any sign of necrosis. The rat cells exhibited first an amoeboid m orphology but progressed at the later stages toward a more mature, ram ified morphology. These results indicate that donor microglia are quit e few in number at first and, at least, do not proliferate actively af ter transplantation. They seem rather to disappear over time. The para llel 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.