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Advancing PD Cell Therapy: Transplanting Cryopreserved iPSC-derived Neurons

December 8, 2015 | 10:00 am CST

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Abstract

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.

About the Speaker

Dr. Dustin Wakeman is an Assistant Professor at Rush University Medical Center where his primary research goals are directed at determining the long-term value of stem cell-based therapeutics in neurodevelopmental and neurodegenerative disease. Dr. Wakeman’s research is primarily focused on pre-clinical testing of dopamine neurons derived from pluripotent stem cells, both human embryonic stem cells and induced pluripotent stem cells (iPSC), as a cell based strategy for dopamine replacement using a rationale course of animal models to predict translational clinical outcome. His lab is also utilizing pluripotent stem cells to develop new strategies to model and treat disorders of the central nervous system. Their goal is to use patient-derived iPSCs as an in vitro platform to model disease-specific phenotypes and develop new drugable targets, as well as in vivo to mimic human disease in the rodent and nonhuman primate brain. Dr. Wakeman received a B.S. in Biology from the University of Illinois at Urbana-Champaign then completed a Ph.D. in Biomedical Sciences at the University of California at San Diego.

Details

Date:
December 8, 2015
Time:
10:00 am CST
Website:
http://labroots.com/webinar/id/177

Venue

Labroots