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Nat Commun. 2016 Oct 14;7:13097. doi: 10.1038/ncomms13097.

Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1.

Author information

1
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
2
Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
3
Group for Antibody Engineering, KAN Research Institute Inc, Kobe 650-0047, Japan.
4
Group for Seed Biologics, KAN Research Institute Inc., Kobe 650-0047, Japan.
5
Group for Neuronal Differentiation and Development, KAN Research Institute Inc., Kobe 650-0047, Japan.
6
Group for Regenerative Medicine, KAN Research Institute Inc., Kobe 650-0047, Japan.
7
Department of Neurosurgery, Kyoto University School of Medicine, Kyoto 606-8507, Japan.

Abstract

Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson's disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM has been developed, but neither marker is specific for ventral midbrain. Here we employ a double selection strategy for cells expressing both CORIN and LMX1A::GFP, and report a cell surface marker to enrich mDA progenitors, LRTM1. When transplanted into 6-OHDA-lesioned rats, human iPSC-derived LRTM1+ cells survive and differentiate into mDA neurons in vivo, resulting in a significant improvement in motor behaviour without tumour formation. In addition, there was marked survival of mDA neurons following transplantation of LRTM1+ cells into the brain of an MPTP-treated monkey. Thus, LRTM1 may provide a tool for efficient and safe cell therapy for PD patients.

PMID:
27739432
PMCID:
PMC5067526
DOI:
10.1038/ncomms13097
[Indexed for MEDLINE]
Free PMC Article

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