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

Bumpei Samata, Daisuke Doi, Kaneyasu Nishimura, Tetsuhiro Kikuchi, Akira Watanabe, Yoshimasa Sakamoto, Jungo Kakuta, Yuichi Ono and Jun Takahashi ()
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Bumpei Samata: Center for iPS Cell Research and Application, Kyoto University
Daisuke Doi: Center for iPS Cell Research and Application, Kyoto University
Kaneyasu Nishimura: Center for iPS Cell Research and Application, Kyoto University
Tetsuhiro Kikuchi: Center for iPS Cell Research and Application, Kyoto University
Akira Watanabe: Center for iPS Cell Research and Application, Kyoto University
Yoshimasa Sakamoto: Group for Antibody Engineering, KAN Research Institute Inc
Jungo Kakuta: Group for Seed Biologics, KAN Research Institute Inc.
Yuichi Ono: Group for Neuronal Differentiation and Development, KAN Research Institute Inc.
Jun Takahashi: Center for iPS Cell Research and Application, Kyoto University

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13097

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