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.

帕金森病 (PD) 的成功细胞疗法需要大量同质的腹侧中脑多巴胺能 (vmDA) 前体。需要通过细胞分选来富集 vmDA 前体，以确保细胞治疗的高安全性和有效性。在这里，我们使用 LMX1A-eGFP 敲入报告人胚胎干细胞，发现了一种新的表面抗原，滋养层糖蛋白 (TPBG)，它优先在 vmDA 前体中表达。TPBG 靶向细胞分选丰富了 FOXA2 ⁺ LMX1A ⁺ vmDA 前体，并有助于通过增加 TH ⁺、NURR1 ⁺和 PITX3 ⁺数量的啮齿动物 PD 模型实现有效的行为恢复移植物中的 vmDA 神经元。此外，在 TPBG ⁺细胞衍生移植物中检测到的增殖细胞比在 TPBG ^-细胞衍生移植物中检测到的增殖细胞少。我们的方法是获得富集的真正vmDA 前体的有效方法，这可以为有效的 PD 治疗开辟一条新途径。