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Cell Stem Cell. 2014 Nov 6;15(5):653-65. doi: 10.1016/j.stem.2014.09.017. Epub 2014 Nov 6.

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

Author information

  • 1Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 22184 Lund, Sweden; Lund Stem Cell Center, Lund University, 22184 Lund, Sweden. Electronic address: shane.grealish@med.lu.se.
  • 2Molecular Imaging Research Centre (MIRCen), Commissariat à l'Energie Atomique (CEA), 92264 Fontenay-aux-Roses, France.
  • 3Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 22184 Lund, Sweden; Lund Stem Cell Center, Lund University, 22184 Lund, Sweden.
  • 4Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 22184 Lund, Sweden.
  • 5Inserm U861, I-Stem, AFM, 91030 Evry Cedex, France; UEVE U861, I-Stem, AFM, 91030 Evry Cedex, France.
  • 6Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 22184 Lund, Sweden; Lund Stem Cell Center, Lund University, 22184 Lund, Sweden. Electronic address: malin.parmar@med.lu.se.

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.

PMID:
25517469
PMCID:
PMC4232736
DOI:
10.1016/j.stem.2014.09.017
[PubMed - indexed for MEDLINE]
Free PMC Article
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