title: Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1.
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.
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Bumpei
authors.initials: B
authors.lastname: Samata
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Doi
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kaneyasu
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Group for Antibody Engineering, KAN Research Institute Inc, Kobe 650-0047, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Group for Seed Biologics, KAN Research Institute Inc., Kobe 650-0047, Japan.
authors.forename: Jungo
authors.initials: J
authors.lastname: Kakuta
authors.affiliation: Group for Neuronal Differentiation and Development, KAN Research Institute Inc., Kobe 650-0047, Japan.|Group for Regenerative Medicine, KAN Research Institute Inc., Kobe 650-0047, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.|Department of Neurosurgery, Kyoto University School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D005260:Female; D000066449:Human Embryonic Stem Cells / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: C533107:LRTOMT protein, human; D011506:Proteins; D012697:Serine Endopeptidases