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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Survival
  • Disease Models, Animal
  • Dopaminergic Neurons / cytology*
  • Dopaminergic Neurons / transplantation*
  • Embryonic Stem Cells / cytology*
  • Fetus / cytology*
  • Humans
  • Male
  • Mesencephalon / embryology
  • Neostriatum / pathology
  • Otx Transcription Factors / metabolism
  • Parkinson Disease / pathology
  • Parkinson Disease / therapy*
  • Rats, Nude
  • Substantia Nigra / pathology
  • Synaptic Transmission
  • Time Factors


  • OTX2 protein, human
  • Otx Transcription Factors