这篇文章详细介绍了一种名为 SphereDiff 的三维培养方法，用于高效、稳定地从人多能干细胞中生成高纯度的中脑多巴胺祖细胞（mDAP），这对于帕金森病（PD）的细胞疗法具有重要意义。研究人员开发了 TX-SISBAR（跨移植单细胞分离条形码）技术，以描绘供体细胞移植后的克隆谱系命运，发现丘脑下部祖细胞主要分化为谷氨酸能神经元，而中脑祖细胞则产生多巴胺能神经元和星形胶质细胞。基于这些谱系见解，他们通过逐步激活 WNT 信号优化了分化方案（SphereDiff stepwise），成功消除了脱靶的丘脑下部祖细胞。最终，使用优化方法生成的供体细胞在 PD 模型小鼠中移植后，产生了功能成熟且几乎纯净的多巴胺能神经元，有效恢复了多巴胺水平和运动功能。References: Zhang X, Wu Z, He H, et al. 3D-generation of high-purity midbrain dopaminergic progenitors and lineage-guided refinement of grafts supports Parkinson’s disease cell therapy[J]. Cell Stem Cell, 2025.
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