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肠道类器官:通往临床应用之路。

Intestinal organoids: The path towards clinical application.

作者信息

Sugihara Hady Yuki, Okamoto Ryuichi, Mizutani Tomohiro

机构信息

Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

Department of Gastroenterology and Hepatology, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

出版信息

Eur J Cell Biol. 2025 Mar;104(1):151474. doi: 10.1016/j.ejcb.2024.151474. Epub 2024 Dec 25.

Abstract

Organoids have revolutionized the whole field of biology with their ability to model complex three-dimensional human organs in vitro. Intestinal organoids were especially consequential as the first successful long-term culture of intestinal stem cells, which raised hopes for translational medical applications. Despite significant contributions to basic research, challenges remain to develop intestinal organoids into clinical tools for diagnosis, prognosis, and therapy. In this review, we outline the current state of translational research involving adult stem cell and pluripotent stem cell derived intestinal organoids, highlighting the advances and limitations in disease modeling, drug-screening, personalized medicine, and stem cell therapy. Preclinical studies have demonstrated a remarkable functional recapitulation of infectious and genetic diseases, and there is mounting evidence for the reliability of intestinal organoids as a patient-specific avatar. Breakthroughs now allow the generation of structurally and cellularly complex intestinal models to better capture a wider range of intestinal pathophysiology. As the field develops and evolves, there is a need for standardized frameworks for generation, culture, storage, and analysis of intestinal organoids to ensure reproducibility, comparability, and interpretability of these preclinical and clinical studies to ultimately enable clinical translation.

摘要

类器官凭借其在体外模拟复杂三维人体器官的能力,给整个生物学领域带来了变革。肠道类器官作为肠道干细胞首次成功的长期培养物,具有尤为重要的意义,这为转化医学应用带来了希望。尽管肠道类器官对基础研究做出了重大贡献,但要将其发展成为用于诊断、预后和治疗的临床工具仍面临挑战。在这篇综述中,我们概述了涉及成体干细胞和多能干细胞来源的肠道类器官的转化研究现状,重点介绍了在疾病建模、药物筛选、个性化医疗和干细胞治疗方面的进展与局限性。临床前研究已经证明肠道类器官能够显著重现感染性和遗传性疾病的功能,并且越来越多的证据表明肠道类器官作为患者特异性替身的可靠性。现在的突破使得能够生成结构和细胞层面都更为复杂的肠道模型,以更好地捕捉更广泛的肠道病理生理学特征。随着该领域的发展和演变,需要针对肠道类器官的生成、培养、储存和分析制定标准化框架,以确保这些临床前和临床研究的可重复性、可比性和可解释性,最终实现临床转化。

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