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Stem Cell Reports. 2017 Sep 12;9(3):868-882. doi: 10.1016/j.stemcr.2017.08.002. Epub 2017 Aug 31.

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

Author information

1
Florey Institute of Neuroscience and Mental Health, Royal Parade, Parkville, VIC 3010, Australia.
2
Florey Institute of Neuroscience and Mental Health, Royal Parade, Parkville, VIC 3010, Australia; Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
3
Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
4
Florey Institute of Neuroscience and Mental Health, Royal Parade, Parkville, VIC 3010, Australia. Electronic address: cparish@unimelb.edu.au.
5
Florey Institute of Neuroscience and Mental Health, Royal Parade, Parkville, VIC 3010, Australia. Electronic address: lachlant@unimelb.edu.au.

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.

KEYWORDS:

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

PMID:
28867345
PMCID:
PMC5599268
DOI:
10.1016/j.stemcr.2017.08.002
[Indexed for MEDLINE]
Free PMC Article

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