Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery.
Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery.
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DOI：
10.3390/ijms22031203
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发表时间：
2021-01-26
影响因子：
5.6
通讯作者：
Tcw J
中科院分区：
文献类型：
--
作者：
Qian L;Tcw J
高通量药物筛选确定了临床试验潜在的有希望的治疗方法。然而，目前的疾病模型与有限的人类患者的生理相关性持续存在的局限性扭曲了药物反应，阻碍了临床疗效的转换，并导致了高临床消耗率。诱导多能干细胞(IPSC)技术的出现彻底改变了药物发现的范式。特别是，基于IPSC的三维(3D)组织工程似乎是一种有前途的体外疾病建模工具，它提供了比传统的二维(2D)培养更复杂的组织结构和微环境线索。在这里，我们讨论基于3D的器官/球体，它们构建了具有进化结构复杂性的高级建模，通过展示2D或动物模型中未察觉的更多人类特有和多样化的病理来推动药物发现。然后，我们将专注于使用人类IPSCs对各种中枢神经系统(CNS)疾病进行建模，从而揭示疾病的发病机制，指导治疗策略的发展。最后，我们将利用从生物工程到Omics技术的多学科方法解决IPSC辅助药物发现的新机遇。尽管面临技术挑战，IPSC通过不同细胞类型的相互作用衍生的细胞体系结构模拟了患者的中枢神经系统，并作为治疗开发和个性化精确医学的平台。
A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.
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DOI：
10.1016/j.mcn.2013.07.007
发表时间：
2013-09
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Burkhardt MF;Martinez FJ;Wright S;Ramos C;Volfson D;Mason M;Garnes J;Dang V;Lievers J;Shoukat-Mumtaz U;Martinez R;Gai H;Blake R;Vaisberg E;Grskovic M;Johnson C;Irion S;Bright J;Cooper B;Nguyen L;Griswold-Prenner I;Javaherian A
通讯作者：
Javaherian A
影响因子：
11
作者：
Alić I;Goh PA;Murray A;Portelius E;Gkanatsiou E;Gough G;Mok KY;Koschut D;Brunmeir R;Yeap YJ;O'Brien NL;Groet J;Shao X;Havlicek S;Dunn NR;Kvartsberg H;Brinkmalm G;Hithersay R;Startin C;Hamburg S;Phillips M;Pervushin K;Turmaine M;Wallon D;Rovelet-Lecrux A;Soininen H;Volpi E;Martin JE;Foo JN;Becker DL;Rostagno A;Ghiso J;Krsnik Ž;Šimić G;Kostović I;Mitrečić D;LonDownS Consortium;Francis PT;Blennow K;Strydom A;Hardy J;Zetterberg H;Nižetić D
通讯作者：
Nižetić D
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
16.2
作者：
Chang, QA;Khare, G;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
16.2
作者：
Alami NH;Smith RB;Carrasco MA;Williams LA;Winborn CS;Han SSW;Kiskinis E;Winborn B;Freibaum BD;Kanagaraj A;Clare AJ;Badders NM;Bilican B;Chaum E;Chandran S;Shaw CE;Eggan KC;Maniatis T;Taylor JP
通讯作者：
Taylor JP