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

Autor:	Wakeman DR; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: dwakeman@rx-gen.com., Hiller BM; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Marmion DJ; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., McMahon CW; Cellular Dynamics International: A Fujifilm Company, Madison, WI 53711, USA., Corbett GT; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Mangan KP; Cellular Dynamics International: A Fujifilm Company, Madison, WI 53711, USA., Ma J; Cellular Dynamics International: A Fujifilm Company, Madison, WI 53711, USA., Little LE; Cellular Dynamics International: A Fujifilm Company, Madison, WI 53711, USA., Xie Z; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Perez-Rosello T; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Guzman JN; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Surmeier DJ; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Kordower JH; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA; The Van Andel Institute, Grand Rapids, MI 49503, USA. Electronic address: jkordowe@rush.edu.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2017 Jul 11; Vol. 9 (1), pp. 149-161. Date of Electronic Publication: 2017 Jun 01.
DOI:	10.1016/j.stemcr.2017.04.033
Abstrakt:	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. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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