Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, N15, W7, Kita-ku, Sapporo 060-8638, Japan.
Cancer Genetic and Stem Cell group, Translational Medical Sciences, School of Medicine, Biodiscovery Institute, Centre for Cancer Sciences, University of Nottingham, NG7 2RD, Nottingham, United Kingdom; Stem Cell biology and Cancer group, Translational Medical Sciences, School of Medicine, Biodiscovery Institute, Centre for Cancer Sciences, University of Nottingham, NG7 2RD, Nottingham, United Kingdom.
Acta Biomater. 2021 Sep 15;132:272-287. doi: 10.1016/j.actbio.2021.05.010. Epub 2021 May 20.
Recent advances in intestinal organoid technologies have paved the way for in vitro recapitulation of the homeostatic renewal of adult tissues, tissue or organ morphogenesis during development, and pathogenesis of many disorders. In vitro modelling of individual patient diseases using organoid systems have been considered key in establishing rational design of personalized treatment strategies and in improving therapeutic outcomes. In addition, the transplantation of organoids into diseased tissues represents a novel approach to treat currently incurable diseases. Emerging evidence from intensive studies suggests that organoid systems' development and functional maturation depends on the presence of an extracellular matrix with suitable biophysical properties, where advanced synthetic hydrogels open new avenues for theoretical control of organoid phenotypes and potential applications of organoids in therapeutic purposes. In this review, we discuss the status, applications, challenges and perspectives of intestinal organoid systems emphasising on hydrogels and their properties suitable for intestinal organoid culture. We provide an overview of hydrogels used for intestinal organoid culture and key factors regulating their biological activity. The comparison of different hydrogels would be a theoretical basis for establishing design principles of synthetic niches directing intestinal cell fates and functions. STATEMENT OF SIGNIFICANCE: Intestinal organoid is an in vitro recapitulation of the gut, which self-organizes from intestinal stem cells and maintains many features of the native tissue. Since the development of this technology, intestinal organoid systems have made significant contribution to rapid progress in intestinal biology. Prevailing methodology for organoid culture, however, depends on animal-derived matrices and suffers from variability and potential risk for contamination of pathogens, limiting their therapeutic application. Synthetic scaffold matrices, hydrogels, might provide solutions to these issues and deepen our understanding on how intestinal cells sense and respond to key biophysical properties of the surrounding matrices. This review provides an overview of developing intestinal models and biomaterials, thereby leading to better understanding of current intestinal organoid systems for both biologists and materials scientists.
近年来，肠道类器官技术的进步为体外重现成人组织的稳态更新、发育过程中组织或器官形态发生以及许多疾病的发病机制铺平了道路。使用类器官系统对个体患者疾病进行体外建模被认为是建立合理的个性化治疗策略设计和改善治疗效果的关键。此外，将类器官移植到患病组织中代表了治疗目前无法治愈疾病的一种新方法。大量研究的新证据表明，类器官系统的发育和功能成熟依赖于具有合适生物物理特性的细胞外基质的存在，其中先进的合成水凝胶为类器官表型的理论控制和类器官在治疗目的中的潜在应用开辟了新途径。在这篇综述中，我们讨论了肠道类器官系统的现状、应用、挑战和前景，重点介绍了水凝胶及其适合肠道类器官培养的特性。我们概述了用于肠道类器官培养的水凝胶和调节其生物活性的关键因素。不同水凝胶的比较将为建立指导肠道细胞命运和功能的合成小生境设计原则提供理论基础。
肠道类器官是肠道的体外再现，它由肠道干细胞自我组织并保持其天然组织的许多特征。自从这项技术发展以来，肠道类器官系统为肠道生物学的快速发展做出了重大贡献。然而，类器官培养的流行方法依赖于动物衍生的基质，并存在着变异性和潜在的病原体污染风险，限制了它们的治疗应用。合成支架基质，如水凝胶，可能为这些问题提供解决方案，并加深我们对肠道细胞如何感知和响应周围基质的关键生物物理特性的理解。这篇综述提供了对肠道模型和生物材料发展的概述，从而使生物学家和材料科学家更好地了解当前的肠道类器官系统。
