Organoid Derivation and Orthotopic Xenotransplantation for Studying Human Intestinal Stem Cell Dynamics
Organoid Derivation and Orthotopic Xenotransplantation for Studying Human Intestinal Stem Cell Dynamics
复制标题
用于研究人肠干细胞动力学的类器官衍生和原位异种移植
DOI：
10.1007/978-1-0716-0747-3_21
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发表时间：
2020
影响因子：
--
通讯作者：
Toshiro Sato
中科院分区：
文献类型：
--
作者：
Shinya Sugimoto;Masayuki Fujii;Toshiro Sato
肠道干细胞在一生中不断自我更新以维持肠道稳态。随着类器官培养系统的出现，我们现在能够在体外无限扩增健康和病变组织来源的人类肠道干细胞，并将其用于各种应用。尽管如此，研究人类肠道干细胞在体内的行为仍然具有挑战性。我们最近开发了一种原位异种移植系统，通过将人类正常结肠类器官移植到小鼠结肠表面，实现了保留干细胞层次的人肠上皮组织的体内重建。我们还将新的生长因子，即胰岛素样生长因子-1 （IGF-1）和成纤维细胞生长因子-2 （FGF-2）引入人肠道类器官的培养条件中，显著提高了类器官的可扩展性和可移植性。通过整合这些最新进展，我们组织了一个组织导向的平台，包括患者来源的肠道类器官的衍生及其原位异种移植。基于人类肠道类器官原位异种移植的研究平台，为研究人类肠道干细胞生物学以及建立新的疾病建模系统提供了有力的工具。
Intestinal stem cells continuously self-renew throughout life to maintain gut homeostasis. With the advent of the organoid culture system, we are now able to indefinitely expand healthy and diseased tissue-derived human intestinal stem cells in vitro and use them for various applications. Nonetheless, investigating the behavior of human intestinal stem cells in vivo still remains challenging. We recently developed an orthotopic xenotransplantation system that realizes in vivo reconstruction of human intestinal epithelial tissue with preserved stem cell hierarchy by engrafting human normal colon organoids onto the mouse colon surface. We also introduced new growth factors, namely, insulin-like growth factor-1 (IGF-1) and fibroblast growth factor-2 (FGF-2), into the culture condition for human intestinal organoids that significantly increase scalability and transfectability of the organoids. By integrating these recent advances, we organized a tissue-oriented platform encompassing derivation of patient-derived intestinal organoids and their orthotopic xenotransplantation. The research platform based on orthotopic xenotransplantation of human intestinal organoids provides a powerful tool for studying human intestinal stem cell biology in native tissue-relevant contexts as well as for establishing novel disease modeling systems.