美国辛辛那提儿童医院医疗中心Michael A. Helmrath团队近期取得重要工作进展，他们研究提出，人多能干细胞来源的类器官在体内修复受损的肠道。相关研究成果2024年9月12日在线发表于《细胞—干细胞》杂志上。

据介绍，组织工程的基本目标是在功能上恢复或改善受损的组织或器官。

研究人员使用体内异种移植物临床前急性损伤模型在小肠中解决了这个问题。研究人员探讨了由人类多能干细胞（hPSC）产生的人类肠道类器官（HIO）修复受损小肠的治疗能力。研究人员假设HIO的细胞复杂性将使其能够维持透壁植入。

为了测试这一点，研究人员开发了一种啮齿动物损伤模型，通过腔内输送，证明了碎片化的HIO在修复后会植入、增殖并持续存在于整个肠道中。不仅观察到粘膜层的恢复，而且在肌层和血管内皮中也观察到显著的掺入。进一步的分析揭示了再生区域内持续存在的细胞类型、近端区域化的保留以及新上皮细胞的功能。

总之，这一研究证明了间充质对肠损伤修复的治疗重要性。

附：英文原文

Title: Human pluripotent stem cell-derived organoids repair damaged bowel in vivo

Author: Holly M. Poling, Nambirajan Sundaram, Garrett W. Fisher, Akaljot Singh, Joseph R. Shiley, Kalpana Nattamai, Vinothini Govindarajah, Alexander R. Cortez, Maksym O. Krutko, Séverine Ménoret, Ignacio Anegon, Magdalena Kasendra, James M. Wells, Christopher N. Mayhew, Takanori Takebe, Maxime M. Mahe, Michael A. Helmrath

Issue&Volume: 2024-09-12

Abstract: The fundamental goal of tissue engineering is to functionally restore or improve damaged tissues or organs. Here we address this in the small bowel using an in vivo xenograft preclinical acute damage model. We investigated the therapeutic capacity of human intestinal organoids (HIOs), which are generated from human pluripotent stem cells (hPSCs), to repair damaged small bowel. We hypothesized that the HIO’s cellular complexity would allow it to sustain transmural engraftment. To test this, we developed a rodent injury model where, through luminal delivery, we demonstrated that fragmented HIOs engraft, proliferate, and persist throughout the bowel following repair. Not only was restitution of the mucosal layer observed, but significant incorporation was also observed in the muscularis and vascular endothelium. Further analysis characterized sustained cell type presence within the regenerated regions, retention of proximal regionalization, and the neo-epithelia’s function. These findings demonstrate the therapeutic importance of mesenchyme for intestinal injury repair.

DOI: 10.1016/j.stem.2024.08.009

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00295-9