Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo

Dustin R. Wakeman, Benjamin M. Hiller, David J. Marmion, Christopher W. McMahon, Grant T. Corbett, Kile P. Mangan, Junyi Ma, Lauren E. Little, Zhong Xie, Tamara Perez-Rosello, Jaime N. Guzman, D. James Surmeier, Jeffrey H. Kordower

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage. To test therapeutic efficacy, cryopreserved iPSC-mDA neurons were transplanted without subculturing into the 6-OHDA-lesioned rat and MPTP-lesioned non-human-primate models of PD. Grafted neurons retained midbrain lineage with extensive fiber innervation in both rodents and monkeys. Behavioral assessment in 6-OHDA-lesioned rats demonstrated significant reversal in functional deficits up to 6 months post transplantation with reinnervation of the host striatum and no aberrant growth, supporting the translational development of pluripotent cell-based therapies in PD.

Original languageEnglish (US)
Pages (from-to)149-161
Number of pages13
JournalStem Cell Reports
Volume9
Issue number1
DOIs
StatePublished - Jul 11 2017
Externally publishedYes

Keywords

  • 6-OHDA
  • cryopreservation
  • iPSC
  • midbrain dopamine neuron
  • MPTP
  • non-human primate
  • Parkinson's disease

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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