生物
胚胎干细胞
祖细胞
移植
祖细胞
多巴胺能
干细胞
帕金森病
体内
疾病
细胞分化
生物信息学
多巴胺
神经科学
细胞生物学
内科学
基因
生物技术
遗传学
医学
作者
Agnete Kirkeby,Sara Nolbrant,Katarína Tiklová,Andreas Heuer,Nigel Kee,Tiago Cardoso,Daniella Rylander Ottosson,Mariah J. Lelos,Pedro Rifes,Stephen B. Dunnett,Shane Grealish,Thomas Perlmann,Malin Parmar
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2017-01-01
卷期号:20 (1): 135-148
被引量:232
标识
DOI:10.1016/j.stem.2016.09.004
摘要
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.
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