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利用类器官构建工程材料以模拟人类肠道发育和癌症。

Engineered materials to model human intestinal development and cancer using organoids.

机构信息

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States; Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States.

Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, United States; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States.

出版信息

Exp Cell Res. 2019 Apr 15;377(1-2):109-114. doi: 10.1016/j.yexcr.2019.02.017. Epub 2019 Feb 19.

Abstract

Human organoids provide constructive in vitro models of human development and disease, as these recapitulate important morphogenetic and functional features of the tissue and species of origin. However, organoid culture technologies often involve the use of biologically-derived materials (e.g. Matrigel™) that do not allow dissection of the independent contributions of the biochemical and biophysical matrix properties to organoid development. Additionally, their inherent lot-to-lot variability and, in the case of Matrigel™, tumor-derived nature limits their applicability as platforms for drug and tissue transplantation therapies. Here, we highlight recent studies that overcome these limitations through engineering of novel biomaterial platforms that (1) allow to study the independent contributions of physicochemical matrix properties to organoid development and their potential for translational therapies, and (2) better recreate the tumor microenvironment for high-throughput, pre-clinical drug development. These studies illustrate how innovative biomaterial constructs can contribute to the modeling of human development and disease using organoids, and as platforms for development of organoid-based therapies. Finally, we discuss the current limitations of the organoid field and how they can potentially be addressed using engineered biomaterials.

摘要

人类类器官为人类发育和疾病提供了具有建设性的体外模型,因为它们再现了组织和起源物种的重要形态发生和功能特征。然而,类器官培养技术通常涉及使用生物衍生材料(例如 Matrigel ™),这些材料无法将生化和生物物理基质特性对类器官发育的独立贡献进行剖析。此外,它们固有的批次间变异性,以及在 Matrigel ™的情况下,肿瘤衍生的性质限制了它们作为药物和组织移植治疗平台的适用性。在这里,我们强调了最近的研究,这些研究通过工程新型生物材料平台克服了这些限制,这些平台(1)允许研究物理化学基质特性对类器官发育的独立贡献及其在转化治疗中的潜力,以及(2)更好地再现肿瘤微环境,以实现高通量、临床前药物开发。这些研究说明了创新的生物材料构建如何有助于使用类器官对人类发育和疾病进行建模,以及作为基于类器官的治疗方法的平台。最后,我们讨论了类器官领域的当前限制,以及如何使用工程生物材料来解决这些限制。

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