Common pitfalls of stem cell differentiation: a guide to improving protocols for neurodegenerative disease models and research.
Common pitfalls of stem cell differentiation: a guide to improving protocols for neurodegenerative disease models and research.
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DOI：
10.1007/s00018-016-2265-3
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发表时间：
2016-10
影响因子：
8
通讯作者：
Ooi, Lezanne
中科院分区：
文献类型：
--
作者：
Engel, Martin;Do-Ha, Dzung;Munoz, Sonia Sanz;Ooi, Lezanne
关键词：
诱导多能干细胞和胚胎干细胞彻底改变了细胞神经科学，提供了在临床前环境中模拟神经系统疾病和测试潜在治疗方法的机会。这些模型的力量已经被广泛讨论，但在这项研究中干细胞分化的潜在陷阱还没有得到很好的描述。我们已经分析了文献，描述了人类多能干细胞分化成三种神经细胞类型，通常用于研究疾病，包括前脑胆碱能神经元阿尔茨海默病，中脑多巴胺能神经元帕金森病和皮质星形胶质细胞神经退行性和精神疾病。公开的分化方案在报道的靶细胞生成效率方面差异很大。此外，通过表达谱和功能对细胞的表征在研究之间不同，并且通常是不充分的，导致高度可变的方案结果。我们将这些信息综合成一个简单的方法，可以在执行或评估分化技术时遵循。最后，我们提出了未来研究的三个考虑因素，包括使用生理O2条件，三维共培养系统和微流体控制喂养周期和生长因子梯度。遵循这些指南将有助于研究人员确保生成强大和有意义的数据，从而充分发挥干细胞分化在疾病建模和再生医学中的潜力。
Induced pluripotent stem cells and embryonic stem cells have revolutionized cellular neuroscience, providing the opportunity to model neurological diseases and test potential therapeutics in a pre-clinical setting. The power of these models has been widely discussed, but the potential pitfalls of stem cell differentiation in this research are less well described. We have analyzed the literature that describes differentiation of human pluripotent stem cells into three neural cell types that are commonly used to study diseases, including forebrain cholinergic neurons for Alzheimer’s disease, midbrain dopaminergic neurons for Parkinson’s disease and cortical astrocytes for neurodegenerative and psychiatric disorders. Published protocols for differentiation vary widely in the reported efficiency of target cell generation. Additionally, characterization of the cells by expression profile and functionality differs between studies and is often insufficient, leading to highly variable protocol outcomes. We have synthesized this information into a simple methodology that can be followed when performing or assessing differentiation techniques. Finally we propose three considerations for future research, including the use of physiological O2 conditions, three-dimensional co-culture systems and microfluidics to control feeding cycles and growth factor gradients. Following these guidelines will help researchers to ensure that robust and meaningful data is generated, enabling the full potential of stem cell differentiation for disease modeling and regenerative medicine.
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影响因子：
4.8
作者：
Correia, Claudia;Serra, Margarida;Espinha, Nuno;Sousa, Marcos;Brito, Catarina;Burkert, Karsten;Zheng, Yunjie;Hescheler, Juergen;Carrondo, Manuel J. T.;Saric, Tomo;Alves, Paula M.
通讯作者：
Alves, Paula M.
影响因子：
2.4
作者：
Consonni S;Leone S;Becchetti A;Amadeo A
通讯作者：
Amadeo A
影响因子：
15.1
作者：
Duan L;Bhattacharyya BJ;Belmadani A;Pan L;Miller RJ;Kessler JA
通讯作者：
Kessler JA
影响因子：
4.9
作者：
Cooke, M. J.;Zahir, T.;Przyborski, S. A.
通讯作者：
Przyborski, S. A.
影响因子：
19.9
作者：
Braskie MN;Thompson PM
通讯作者：
Thompson PM