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首页> 美国卫生研究院文献>Cellular and Molecular Gastroenterology and Hepatology >Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche
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Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche

机译：概述肠道干细胞生态位的生物工程系统和设计器矩阵

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The relationship between intestinal stem cells (ISCs) and the surrounding niche environment is complex and dynamic. Key factors localized at the base of the crypt are necessary to promote ISC self-renewal and proliferation, to ultimately provide a constant stream of differentiated cells to maintain the epithelial barrier. These factors diminish as epithelial cells divide, migrate away from the crypt base, differentiate into the postmitotic lineages, and end their life span in approximately 7 days when they are sloughed into the intestinal lumen. To facilitate the rapid and complex physiology of ISC-driven epithelial renewal, in vivo gradients of growth factors, extracellular matrix, bacterial products, gases, and stiffness are formed along the crypt-villus axis. New bioengineered tools and platforms are available to recapitulate various gradients and support the stereotypical cellular responses associated with these gradients. Many of these technologies have been paired with primary small intestinal and colonic epithelial cells to re-create select aspects of normal physiology or disease states. These biomimetic platforms are becoming increasingly sophisticated with the rapid discovery of new niche factors and gradients. These advancements are contributing to the development of high-fidelity tissue constructs for basic science applications, drug screening, and personalized medicine applications. Here, we discuss the direct and indirect evidence for many of the important gradients found in vivo and their successful application to date in bioengineered in vitro models, including organ-on-chip and microfluidic culture devices.
机译：肠干细胞（ISC）与周围环境之间的关系是复杂而动态的。位于隐窝底部的关键因子对于促进ISC自我更新和增殖是必不可少的，以最终提供恒定的分化细胞流以维持上皮屏障。随着上皮细胞分裂，从隐窝基部迁移，分化为有丝分裂后谱系，并在它们掉入肠腔中的大约7天的生命期结束，这些因素会减少。为了促进ISC驱动的上皮更新的快速和复杂的生理过程，沿隐窝-绒毛轴形成了生长因子，细胞外基质，细菌产物，气体和硬度的体内梯度。新的生物工程工具和平台可用于概括各种梯度并支持与这些梯度相关的定型细胞反应。这些技术中的许多已与原代小肠和结肠上皮细胞配对，以重新创建正常生理或疾病状态的特定方面。随着新的利基因素和梯度的迅速发现，这些仿生平台变得越来越复杂。这些进步有助于开发用于基础科学应用，药物筛选和个性化医学应用的高保真组织构造。在这里，我们讨论了在活体内发现的许多重要梯度的直接和间接证据，以及它们迄今为止在体外模型的生物工程中成功应用的成功经验，包括芯片上的器官和微流体培养装置。

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