Advancing PD Cell Therapy: Transplanting Cryopreserved iPSC-derived Neurons

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Cellular Dynamics

Cryopreservation of post-mitotic, induced pluripotent stem cell-derived midbrain lineage dopamine neurons (iPSC-mDA) is a significant advancement for cell therapy in Parkinson’s disease. Here, we demonstrate that cryopreserved iPSC-mDA neurons are reliably thawed with excellent viability and maintain biochemical and physiological signatures indicative of human midbrain dopamine neurons. We also examined the engraftment potential of iPSC-mDA neurons after transplantation into both the rodent brain up to 6-months post-grafting and the nonhuman primate brain up to 3-months post-transplantation. Immunohistochemical analysis demonstrated robust graft survival and maintenance of the midbrain dopaminergic phenotype with extensive fiber innervation into the host. A long-term functional study revealed significant reversal in motor deficits in the 6-OHDA-lesioned rat model of Parkinson’s disease that persisted for up to 6-months post-transplantation. Moreover, we found no evidence of cell proliferation, indicating safety in our initial studies. IND-enabling studies are currently underway to ascertain whether cryopreserved iPSC-mDA neurons are both safe and efficacious at longer time-points in both rodent and nonhuman primate models of Parkinson’s disease. These results indicate considerable promise for the development of pluripotent cell-based therapies in Parkinson’s disease.