Association between integrin-dependent migration capacity of neural stem cells in vitro and anatomical repair following transplantation

In previous transplantation studies using neural stem cell lines immortaliz ed by the temperature-sensitive SV40 large T-antigen, we have shown that an imals with experimental hippocampal lesions resulting from four vessel occl usion recover spatial memory functions more effectively when grafted with t he MHP36 cell line than with the MHP15 cell line [Gray et al. (1999). Philo s. Trans. R. Soc. London Biol. Sci. 354: 1407-1421]. In the present study, we have investigated the cellular and molecular basis of these differences in repair capacity both in vivo and in vitro. Using the same model of hippo campal damage we have shown that following transplantation MHP36 cells migr ate and align within the damaged CA1 of the ipsilateral hippocampus. MHP15 cells, in contrast, migrate in a more indiscriminate pattern that does not reflect the anatomy of the region. To analyze the migratory properties of t hese two cell lines in more detail, we performed migration assays at a nonp ermissive temperature on the extracellular matrix substrates laminin, fibro nectin, and vitronectin. These showed that MHP36 cells have a greater migra tion potential than the MHP15 cells. While the pattern of cell surface extr acellular matrix receptors of the integrin family was identical in both cel l lines, the different degrees of migration on vitronectin were both blocke d by inhibitors of alphaV integrins. Differences in integrin signaling ther efore contribute to the greater migration potential of the repairing MHP36 cell line.