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Abstract：
Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation of immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, and predicting the long-term graft outcome already at the progenitor stage remains a challenge. Here, we took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson\'s disease through gene expression analysis of >30 batches of grafted human embryonic stem cell (hESC)-derived progenitors. We found that many of the commonly used markers did not accurately predict in vivo subtype-specific maturation. Instead, we identified a specific set of markers associated with the caudal midbrain that correlate with high dopaminergic yield after transplantation in vivo. Using these markers, we developed a good manufacturing practice (GMP) differentiation protocol for highly efficient and reproducible production of transplantable dopamine progenitors from hESCs.
摘要：
干细胞治疗神经退行性疾病有望很快达到临床试验。目前正在开发的大多数方法都涉及移植未成熟的祖细胞，这些祖细胞随后在体内经历表型和功能成熟，预测已经在祖细胞阶段的长期移植结果仍然是一个挑战。这里,我们通过对>30批移植人类胚胎干细胞(hESC)衍生祖细胞的基因表达分析,采用无偏方法鉴定了多巴胺神经元祖细胞中表达的与帕金森病动物模型移植结果相关的预测标志物。我们发现许多常用的标记不能准确预测体内亚型特异性成熟。相反，我们确定了一组与尾中脑相关的特异性标志物，这些标志物与体内移植后的多巴胺能高产量相关。使用这些标记，我们开发了一个良好的生产规范（GMP）分化方案，用于高效和可重复地从hESCs生产可移植的多巴胺祖细胞。
