Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip.
Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip.
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DOI：
10.1007/s12015-021-10205-y
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发表时间：
2022-08
影响因子：
4.8
通讯作者：
Wang XQ
中科院分区：
文献类型：
--
作者：
Li XG;Chen MX;Zhao SQ;Wang XQ
肠道功能障碍通常是由特定基因、微生物群或微环境因素的异常驱动的，这些因素通常在个体之间存在差异，肠道生理和病理也是如此。因此，有必要制定个性化的治疗策略，目前由于缺乏模拟肠道模型而受到限制。成熟的人肠黏膜被单层柱状上皮细胞覆盖，这些细胞来源于肠干细胞（ISCs）。器官的复杂性极大地增加了忠实地模仿体内微环境的难度。然而，模拟肠道模型将成为个性化药物筛选不可或缺的基础。本文综述了传统二维模型、肠道类器官模型和当前微流控肠道芯片模型的优缺点。总结了主要的技术策略，提出了一种用于个性化肠道医学的先进微流控初级IOAC模型。在该模型中，从个体中分离出初级ISCs和微生物组，并在多通道微流控芯片中共同培养，以建立微工程肠道装置。该装置可以真实地模拟体内流体流动、蠕动运动、宿主-微生物串扰和多细胞类型的相互作用。此外，ISCs可以在播种前进行基因编辑，监测传感器和后期分析能力也可以纳入该设备，以实现高通量和快速的药物研究。我们还讨论了微流控平台的潜在未来应用和挑战。细胞生物学、生物材料和组织工程的发展将推动模拟肠道的进步，为未来的个性化医疗做出重大贡献。肠道是消化、吸收和代谢的主要器官，也是宿主-共生菌群相互作用和粘膜免疫的主要场所。尽管原生小肠上皮组织的生理三维特征已经得到了很好的记录，但器官的复杂性极大地增加了忠实地模拟体内微环境的难度。基于肠道干细胞的微流体肠道芯片模型能够真实地模拟体内流体流动、蠕动运动、宿主-微生物串扰和多细胞类型的相互作用，这将做出重大贡献。
Intestinal dysfunction is frequently driven by abnormalities of specific genes, microbiota, or microenvironmental factors, which usually differ across individuals, as do intestinal physiology and pathology. Therefore, it’s necessary to develop personalized therapeutic strategies, which are currently limited by the lack of a simulated intestine model. The mature human intestinal mucosa is covered by a single layer of columnar epithelial cells that are derived from intestinal stem cells (ISCs). The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments. However, a simulated intestine model will serve as an indispensable foundation for personalized drug screening. In this article, we review the advantages and disadvantages of conventional 2-dimensional models, intestinal organoid models, and current microfluidic intestine-on-a-chip (IOAC) models. The main technological strategies are summarized, and an advanced microfluidic primary IOAC model is proposed for personalized intestinal medicine. In this model, primary ISCs and the microbiome are isolated from individuals and co-cultured in a multi-channel microfluidic chip to establish a microengineered intestine device. The device can faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions. Moreover, the ISCs can be genetically edited before seeding, and monitoring sensors and post-analysis abilities can also be incorporated into the device to achieve high-throughput and rapid pharmaceutical studies. We also discuss the potential future applications and challenges of the microfluidic platform. The development of cell biology, biomaterials, and tissue engineering will drive the advancement of the simulated intestine, making a significant contribution to personalized medicine in the future. The intestine is a primary organ for digestion, absorption, and metabolism, as well as a major site for the host-commensal microbiota interaction and mucosal immunity. The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments, though physiological 3-dimensional of the native small intestinal epithelial tissue has been well documented. An intestinal stem cells-based microfluidic intestine-on-a-chip model that faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions will make a significant contribution.
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影响因子：
3.6
作者：
Derricott H;Luu L;Fong WY;Hartley CS;Johnston LJ;Armstrong SD;Randle N;Duckworth CA;Campbell BJ;Wastling JM;Coombes JL
通讯作者：
Coombes JL
影响因子：
64.8
作者：
Ayyaz, Arshad;Kumar, Sandeep;Gregorieff, Alex
通讯作者：
Gregorieff, Alex
影响因子：
46.9
作者：
Bhatia, Sangeeta N.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
8.8
作者：
Co, Julia Y.;Margalef-Catala, Mar;Amieva, Manuel R.
通讯作者：
Amieva, Manuel R.
DOI：
10.1016/j.jcmgh.2017.12.010
发表时间：
2018
影响因子：
7.2
作者：
Bein A;Shin W;Jalili-Firoozinezhad S;Park MH;Sontheimer-Phelps A;Tovaglieri A;Chalkiadaki A;Kim HJ;Ingber DE
通讯作者：
Ingber DE