Successful cell therapy for Parkinson’s disease (PD) requires large numbers of homogeneous ventral mesencephalic dopaminergic (vmDA) precursors. Enrichment of vmDA precursors via cell sorting is required to ensure high safety and efficacy of the cell therapy. Here, using LMX1A-eGFP knock-in reporter human embryonic stem cells, we discovered a novel surface antigen, trophoblast glycoprotein (TPBG), which was preferentially expressed in vmDA precursors. TPBG-targeted cell sorting enriched FOXA2+LMX1A+ vmDA precursors and helped attain efficient behavioral recovery of rodent PD models with increased numbers of TH+, NURR1+, and PITX3+ vmDA neurons in the grafts. Additionally, fewer proliferating cells were detected in TPBG+ cell-derived grafts than in TPBG− cell-derived grafts. Our approach is an efficient way to obtain enriched bona fide vmDA precursors, which could open a new avenue for effective PD treatment.
Bibliographical noteFunding Information:
D.-W.K. was supported by the Korea Health Technology R&D Project Grant (HI18C0829) through the Korea Health Industry Development Institute, founded by the Ministry of Health & Welfare. D.-Y.H. and M.S.C. were supported by a grant (HI18C0096) from the Ministry of Health and Welfare. This study was carried out in part in the Yonsei Advanced Imaging Center in cooperation with Carl Zeiss Microscopy, Yonsei University College of Medicine.
© 2021, The Author(s).
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience