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Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.

Abstract
Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson's disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson's disease.
AuthorsShane Grealish, Elsa Diguet, Agnete Kirkeby, Bengt Mattsson, Andreas Heuer, Yann Bramoulle, Nadja Van Camp, Anselme L Perrier, Philippe Hantraye, Anders Björklund, Malin Parmar
JournalCell stem cell (Cell Stem Cell) Vol. 15 Issue 5 Pg. 653-65 (Nov 06 2014) ISSN: 1875-9777 [Electronic] United States
PMID25517469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • OTX2 protein, human
  • Otx Transcription Factors
Topics
  • Animals
  • Axons (metabolism)
  • Cell Survival
  • Disease Models, Animal
  • Dopaminergic Neurons (cytology, transplantation)
  • Embryonic Stem Cells (cytology)
  • Fetus (cytology)
  • Humans
  • Male
  • Mesencephalon (embryology)
  • Neostriatum (pathology)
  • Otx Transcription Factors (metabolism)
  • Parkinson Disease (pathology, therapy)
  • Rats, Nude
  • Substantia Nigra (pathology)
  • Synaptic Transmission
  • Time Factors

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