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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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