A PITX3-EGFP Reporter Line Reveals Connectivity of Dopamine and Non-dopamine Neuronal Subtypes in Grafts Generated from Human Embryonic Stem Cells

Jonathan C. Niclis, Carlos W. Gantner, Cameron P.J. Hunt, Jessica A. Kauhausen, Jennifer C. Durnall, John M. Haynes, Colin W. Pouton, Clare L. Parish, Lachlan H. Thompson

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Development of safe and effective stem cell-based therapies for brain repair requires an in-depth understanding of the in vivo properties of neural grafts generated from human stem cells. Replacing dopamine neurons in Parkinson's disease remains one of the most anticipated applications. Here, we have used a human PITX3-EGFP embryonic stem cell line to characterize the connectivity of stem cell-derived midbrain dopamine neurons in the dopamine-depleted host brain with an unprecedented level of specificity. The results show that the major A9 and A10 subclasses of implanted dopamine neurons innervate multiple, developmentally appropriate host targets but also that the majority of graft-derived connectivity is non-dopaminergic. These findings highlight the promise of stem cell-based procedures for anatomically correct reconstruction of specific neuronal pathways but also emphasize the scope for further refinement in order to limit the inclusion of uncharacterized and potentially unwanted cell types.

Original languageEnglish
Pages (from-to)868-882
Number of pages15
JournalStem Cell Reports
Volume9
Issue number3
DOIs
Publication statusPublished - 12 Sep 2017

Keywords

  • cell-replacement therapy
  • dopamine
  • embryonic stem cells
  • integration
  • PITX3
  • regeneration
  • transplantation

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