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胃肠道组织工程的现状与临床应用:一项系统化叙述性综述

英文原题:Current status and clinical applications of tissue engineering of the gastrointestinal tract: a systematized narrative review.

PubMed 2023/11/07(内容时间) Front Gastroenterol (Lausanne) Q4 · IF 1.2(JCR 2025)

研究概要

组织工程方法在动物模型中已被广泛探索用于修复食管、胃、肠道、直肠和肛门等各种类型的GI缺损,并取得了有希望的结果。此外,成功的人体试验已证明使用这些创新方法重建食管、直肠和肛门缺损的可行性。间充质干细胞、去细胞化、类器官和细胞片等技术最具前景,也更接近临床转化。胃肠外科与再生医学之间的合作有望在未来带来新的治疗模式。

研究思路结论见上方概要

自再生医学问世以来,胃肠道的组织工程已在实验室动物和人类中进行了广泛研究。各种生物支架和细胞来源已被尝试用于修复或重建不同的胃肠道缺陷。该领域的成就引领了治疗胃肠道疾病的新方法,并规避了当前疗法相关的并发症发病率。

本综述旨在描述GIT组织工程的最新进展,重点关注具有临床应用潜力的技术。

在Ovid MEDLINE ALL中进行了文献检索,以寻找相关研究(2000年至2023年9月),使用的关键词为“组织工程”、“支架”、“类器官”、“细胞治疗”、“食管”、“胃”、“小肠”、“结肠”、“直肠”和“肛门”。如果研究为英文撰写的体内动物研究或临床研究,且探讨了用于治疗GIT缺陷的组织工程,则纳入这些文章。

初步检索共识别出836篇文章。去除重复文献并经过摘要和全文筛选后,最终纳入48篇文章进行综述。迄今为止,许多关于食管缺损的研究描述了在动物和人类中使用自体细胞片覆盖部分厚度缺损以及使用脱细胞支架闭合全层缺损的成功经验。有限数量的报道还证明了利用自体多能细胞和支架从头器官发生食管以修复短段环形食管缺损。在胃部,多项动物研究报道了利用多能细胞和/或支架再生胃上皮以修复部分和全层缺损的可行性。一项研究观察到使用聚合物上类器官方法再生全层胃缺损。同样,在肠道中,多能细胞和支架被证明能有效修复部分和全层缺损。动物实验已通过聚合物上类器官方法产生了组织工程小肠(TESI)。此外,在直肠和肛门中,伴或不伴生物支架的间充质干细胞疗法已显示出治疗全层缺损的前景,这在多项人体试验中得到了证实。

展开英文摘要原文

BACKGROUND: Since the advent of regenerative medicine, tissue engineering of the gastrointestinal tract (GIT) has been extensively studied in laboratory animals and humans. Various biologic scaffolds and cell sources have been trialed to repair or reconstruct different GIT defects. Achievements in this field have led to novel approaches in curing GIT diseases and circumventing the morbidity-related complications associated with current therapy. OBJECTIVE: This review aims to describe recent advances in GIT tissue engineering, with an emphasis on technologies with potential for clinical use. METHODS: A literature search was conducted in Ovid MEDLINE ALL for relevant studies (2000-September 2023) using the keywords "tissue-engineering", "scaffolds", "organoids", "cell-therapy", "esophagus", "stomach", "small intestine", "colon", "rectum", and "anus". Articles were included if they were in vivo animal studies or clinical studies written in English that investigated tissue engineering for treating GIT defects. RESULTS: A total of 836 articles were identified in the initial search. Following duplicate removal, abstract, and full-text screening, 48 articles were included in the final review. Many studies on esophageal defects thus far have described the success of covering partial-thickness defects with autologous cell sheets and closing full-thickness defects with decellularized scaffolds in both animals and humans. A limited number of reports have also demonstrated the de novo organogenesis of the esophagus to repair short-segment circumferential esophageal defects with autologous pluripotent cells and scaffolds. In the stomach, multiple animal studies have reported on the feasibility of gastric epithelium regeneration using multipotent cells and/or scaffolds to correct partial- and full-thickness defects. One study observed the regeneration of whole-layer stomach defects using the organoids-on-polymer approach. Similarly, in the intestine, pluripotent cells and scaffolds were shown to effectively repair both partial- and full-thickness defects. Animal experiments have produced tissue-engineered small intestines (TESI) with the organoids-on-polymer approach. Furthermore, in the rectum and anus, mesenchymal stem cell therapies with or without bioscaffolds have shown promise for treating full-thickness defects, as demonstrated in multiple human trials. CONCLUSION: Tissue-engineering approaches for repairing various types of GI defects in the esophagus, stomach, intestines, rectum, and anus have been extensively explored in animal models, with promising outcomes. Moreover, successful human trials have demonstrated the feasibility of reconstructing esophageal, rectal, and anal defects using these innovative approaches. Technologies such as mesenchymal stem cells, decellularization, organoids, and cell sheets are the most promising and closer to clinical translation. Collaboration between gastrointestinal surgery and regenerative medicine is expected to bring about novel therapeutic modalities in the future.

论文信息

作者
Liu Y、Chong L、Read M
第一作者单位
Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC, Australia.Australia
通讯作者单位
Department of Surgery, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, Australia.Australia
文献类型
综述
期刊
Frontiers in gastroenterology (Lausanne, Switzerland)2023
原文标识
PubMed 41821809 · DOI 10.3389/fgstr.2023.1277094