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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.

Grealish, Shane LU ; Diguet, Elsa; Kirkeby, Agnete LU ; Mattsson, Bengt LU ; Heuer, Andreas LU ; Bramoulle, Yann; Van Camp, Nadja; Perrier, Anselme L; Hantraye, Philippe and Björklund, Anders LU , et al. (2014) In Cell Stem Cell 15(5). p.653-665
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... (More)
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. (Less)
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Cell Stem Cell
volume
15
issue
5
pages
653 - 665
publisher
Cell Press
external identifiers
  • pmid:25517469
  • wos:000345012700017
  • scopus:84922662454
ISSN
1934-5909
DOI
10.1016/j.stem.2014.09.017
language
English
LU publication?
yes
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c11e43ac-0348-4574-ba4d-14c97648d7cd (old id 4908060)
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http://www.ncbi.nlm.nih.gov/pubmed/25517469?dopt=Abstract
date added to LUP
2015-01-07 15:58:35
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2017-11-19 03:16:33
@article{c11e43ac-0348-4574-ba4d-14c97648d7cd,
  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.},
  author       = {Grealish, Shane and Diguet, Elsa and Kirkeby, Agnete and Mattsson, Bengt and Heuer, Andreas and Bramoulle, Yann and Van Camp, Nadja and Perrier, Anselme L and Hantraye, Philippe and Björklund, Anders and Parmar, Malin},
  issn         = {1934-5909},
  language     = {eng},
  number       = {5},
  pages        = {653--665},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {Human ESC-Derived Dopamine Neurons Show Similar Preclinical Efficacy and Potency to Fetal Neurons when Grafted in a Rat Model of Parkinson's Disease.},
  url          = {http://dx.doi.org/10.1016/j.stem.2014.09.017},
  volume       = {15},
  year         = {2014},
}