Implications and limitations of cellular reprogramming for psychiatric drug development.
Implications and limitations of cellular reprogramming for psychiatric drug development.
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DOI：
10.1038/emm.2013.124
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发表时间：
2013-11-15
影响因子：
12.8
通讯作者：
Snyder, Evan Y.
中科院分区：
文献类型：
--
作者：
Tobe, Brian T. D.;Brandel, Michael G.;Nye, Jeffrey S.;Snyder, Evan Y.
关键词：
来源于患者体细胞的人诱导多能干细胞（hiPSC）为在精神疾病状态下对神经（和其他）细胞的生理学进行体外建模开辟了可能性。技术开发早期阶段的问题包括（1）建立来自充分表型化患者的细胞库，（2）简化费力、昂贵的hiPSC衍生和表征，（3）评估通过重编程引入的突变或其他改变是否混淆解释，（4）开发针对相关细胞类型的有效分化策略，（5）鉴定对周期性、应激诱导或复发-缓解性疾病有意义的可辨别的细胞表型，（6）将表型转化为适合于全基因组机制研究或大集合化合物测试的筛选测定，以及（7）控制低样本数中与疾病特异性相关的变异性。从临床、遗传和神经影像学特征良好的患者中获得的重编程材料的协调工作正在开始，初步研究已经开始确定细胞表型。最后，已经发现几种精神药物改变体外重编程效率，这表明将hiPSC应用于精神疾病的进一步复杂性，或者某些药物对神经分化的影响比通常认为的更大。尽管存在这些挑战，但利用hiPSC的研究最终可能会填补发现新疗法的转化管道中的重要利基。
Human-induced pluripotent stem cells (hiPSCs) derived from somatic cells of patients have opened possibilities for in vitro modeling of the physiology of neural (and other) cells in psychiatric disease states. Issues in early stages of technology development include (1) establishing a library of cells from adequately phenotyped patients, (2) streamlining laborious, costly hiPSC derivation and characterization, (3) assessing whether mutations or other alterations introduced by reprogramming confound interpretation, (4) developing efficient differentiation strategies to relevant cell types, (5) identifying discernible cellular phenotypes meaningful for cyclic, stress induced or relapsing–remitting diseases, (6) converting phenotypes to screening assays suitable for genome-wide mechanistic studies or large collection compound testing and (7) controlling for variability in relation to disease specificity amidst low sample numbers. Coordination of material for reprogramming from patients well-characterized clinically, genetically and with neuroimaging are beginning, and initial studies have begun to identify cellular phenotypes. Finally, several psychiatric drugs have been found to alter reprogramming efficiency in vitro, suggesting further complexity in applying hiPSCs to psychiatric diseases or that some drugs influence neural differentiation moreso than generally recognized. Despite these challenges, studies utilizing hiPSCs may eventually serve to fill essential niches in the translational pipeline for the discovery of new therapeutics.
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DOI：
10.1523/jneurosci.1758-09.2009
发表时间：
2009-09-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Covington HE 3rd;Maze I;LaPlant QC;Vialou VF;Ohnishi YN;Berton O;Fass DM;Renthal W;Rush AJ 3rd;Wu EY;Ghose S;Krishnan V;Russo SJ;Tamminga C;Haggarty SJ;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
46.9
作者：
Deng, Jie;Shoemaker, Robert;Xie, Bin;Gore, Athurva;LeProust, Emily M.;Antosiewicz-Bourget, Jessica;Egli, Dieter;Maherali, Nimet;Park, In-Hyun;Yu, Junying;Daley, George Q.;Eggan, Kevin;Hochedlinger, Konrad;Thomson, James;Wang, Wei;Gao, Yuan;Zhang, Kun
通讯作者：
Zhang, Kun
从脐带基质和羊膜间充质细胞产生人类诱导多能干细胞
影响因子：
4.8
作者：
Cai, Jinglei;Li, Wen;Pei, Duanqing
通讯作者：
Pei, Duanqing
DOI：
10.1073/pnas.0601992103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Encinas, Juan M.;Vaahtokari, Anne;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori
影响因子：
46.9
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
通讯作者：
Melton, Douglas A.