Preclinical Studies of Induced Pluripotent Stem Cell-Derived Astrocyte Transplantation in ALS.

摘要

We have now created numerous iPS cell lines from ALS patient samples and have characterized their long-term differentiation into astroglia. We now have data from the in vivo transplantation of these astroglial progenitors into rat spinal cords. We have characterized several controls and an ALS cell line with regard to their survival, differentiation, migration, and phenotypic effects on the host animals. Our data demonstrate that there are differences amongst the cell lines with regard to these properties but we have not appreciated obvious differences with regard to ALS cells when compared with control astroglial cells. Finally, we have demonstrated, in preparation for our therapeutic approaches, that these glial progenitor cells continue to mature into astrocytes following transplantation but that their survival is significantly reduced when compared with previous studies using human glial restricted precursors. Given this poor survival (5% of transplanted iPSC-derived astrocytes), we have used human fetally-derived glial restricted precursors to understand how the ALS host environment influences transplanted cells.