Yoo Jeong-Eun, Lee Dongjin R, Park Sanghyun, Shin Hye-Rim, Lee Kun Gu, Kim Dae-Sung, Jo Mi-Young, Eom Jang-Hyeon, Cho Myung Soo, Hwang Dong-Youn, Kim Dong-Wook
Department of Physiology, Yonsei University College of Medicine, Seoul, South Korea.
Severance Biomedical Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
NPJ Parkinsons Dis. 2021 Jul 19;7(1):61. doi: 10.1038/s41531-021-00204-8.
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 FOXA2LMX1A 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.
成功的帕金森病（PD）细胞疗法需要大量同质的腹侧中脑多巴胺能（vmDA）前体细胞。通过细胞分选富集vmDA前体细胞对于确保细胞疗法的高安全性和有效性是必要的。在此，我们使用LMX1A-eGFP基因敲入报告人胚胎干细胞，发现了一种新的表面抗原，即滋养层糖蛋白（TPBG），其在vmDA前体细胞中优先表达。靶向TPBG的细胞分选富集了FOXA2+LMX1A+ vmDA前体细胞，并有助于啮齿动物PD模型实现有效的行为恢复，移植中TH、NURR1和PITX3 vmDA神经元数量增加。此外，在TPBG细胞衍生的移植物中检测到的增殖细胞比非TPBG细胞衍生的移植物中更少。我们的方法是获得富集的真正vmDA前体细胞的有效途径，这可能为有效的PD治疗开辟一条新途径。
