Organoid Medicine for Inflammatory Bowel Disease
Organoid Medicine for Inflammatory Bowel Disease
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治疗炎症性肠病的类器官药物
DOI：
10.1093/stmcls/sxab020
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发表时间：
2022
期刊：
影响因子：
5.2
通讯作者：
Sato Toshiro
中科院分区：
文献类型：
--
作者：
Wakisaka Yusuke;Sugimoto Shinya;Sato Toshiro
炎症性肠病（IBD）是一种病因不明的慢性复发-缓解型胃肠道炎症性疾病，其发病率在全球范围内呈上升趋势。免疫调节治疗剂如生物制剂和小分子抑制剂的最新进展改善了IBD患者的预后。然而，一些患者对这些免疫调节疗法是难治性和耐药性的，需要新的疗法。鉴于肠上皮细胞在IBD发病机制中的重要性，难以长期培养肠上皮细胞（IEC）仍然是IBD研究的障碍。在过去的15年中，已经鉴定出肠干细胞，并且已经阐明了维持肠干细胞所需的体内微环境（称为生态位），从而使永久培养IEC成为可能。在体外重述生态位，肠上皮形成称为类器官的三维结构，其模拟体内的肠上皮。肠上皮细胞在肠屏障和免疫调节功能中起重要作用，并且充当将肠腔与身体分开的物理结构。最近的研究表明，肠上皮的功能破坏与IBD的发病机制密切相关，使用类器官进行IBD研究已引起关注。在这篇综述中，我们讨论了成人组织来源的类器官培养技术的应用，以阐明IBD的发病机制，并开发新的治疗方法，包括再生治疗。
Inflammatory bowel disease (IBD) is a chronic relapsing-remitting inflammatory disease of the gastrointestinal tract with an unknown etiology, and its incidence is increasing worldwide. Recent advances in immunomodulatory therapeutic agents such as biologics and small-molecule inhibitors have improved the prognosis of patients with IBD. However, some patients are refractory and resistant to these immunomodulatory therapies, and new therapies are needed. Given the importance of the intestinal epithelium in IBD pathogenesis, the difficulty of culturing intestinal epithelial cells (IECs) for long periods remains an obstacle in IBD research. Over the past 15 years, intestinal stem cells have been identified, and the in vivo microenvironment, called the niche, required for their maintenance has been elucidated, making the permanent culture of IECs possible. Recapitulating the niche in vitro, the intestinal epithelium forms 3-dimensional structures called organoids that simulate the intestinal epithelium in vivo. The intestinal epithelium plays an important role in the intestinal barrier and immunomodulatory functions and serves as a physical structure that separates the intestinal lumen from the body. Recent studies have revealed that functional disruption of the intestinal epithelium is closely related to the pathogenesis of IBD, and IBD research using organoids has attracted attention. In this review, we discuss the application of adult tissue-derived organoids culture technology to elucidate the pathogenesis of IBD and to develop novel therapies, including regenerative treatments.