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。在这里，我们使用体内异种移植临床前急性损伤模型在小肠中解决这个问题。我们研究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。我们假设 HIO 的细胞复杂性使其能够维持跨壁植入。为了测试这一点，我们开发了一种啮齿动物损伤模型，通过腔内递送，我们证明了碎片化的 HIO 在修复后植入、增殖并持续存在于整个肠道中。不仅观察到粘膜层的恢复，而且还在肌层和血管内皮中观察到显着的合并。进一步的分析表征了再生区域内存在的持续细胞类型、近端区域化的保留以及新上皮的功能。这些发现证明了间充质对于肠道损伤修复的治疗重要性。版权所有 © 2024 Elsevier Inc. 保留所有权利。

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.Copyright © 2024 Elsevier Inc. All rights reserved.