Different behaviour of implanted stem cells in intact and lesioned forebrain cortices

Cell-replacement therapy promises a useful tool to regenerate compromised brain tissue, but the interaction between grafted cells and host tissues is not well understood. In these studies, the fates of neuroectodermal stem cells were compared in 'healthy' or damaged mouse forebrains. One-cell derived, fluorescent GFP-4C neural stem cells were implanted into normal and cold-lesioned mouse cortices. The fates of implanted cells were followed by histological and immunocytochemical assays for a 55-day postimplantation period. Cells were recultivated from lesioned cortices and characterized by cell cycle parameters, chromosome numbers, immunocytochemical markers and in vitro inducibility. Their intracerebral fates were checked upon re-implanting into 'healthy' mouse brain cortices. GFP-4C cells, giving rise to neurones and astrocytes upon in vitro induction, failed to differentiate in either normal or lesioned cortical tissues. The rate of proliferation and the length of the survival, however, depended on the host environment, markedly. In intact cortices, implanted cells formed compact, isolated aggregates and their survival did not exceed 4 weeks. In compromised cortices, GFP-4C cells survived longer than 8 weeks and repopulated the decayed region. The morphology, viability, immunocytochemical properties, in vitro inducibility and chromosome number of cells recultivated from lesioned cortices were identical to those of the master cells. Long-term survival and repopulating capability were due to signals present in the lesioned, but missing from the intact cortical environment. The results underline the importance of host environment in the fate determination of grafted cells and emphasize the need to understand the 'roles' of recipient tissues for potential cell-replacement methodologies.