Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45219, USA; Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45219, USA.
Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45219, USA.
Cell Stem Cell. 2024 Oct 3;31(10):1513-1523.e7. doi: 10.1016/j.stem.2024.08.009. Epub 2024 Sep 12.
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.
组织工程的根本目标是功能性地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物急性损伤模型来解决小肠的这一问题。我们研究了人类肠类器官（HIO）的治疗能力，HIO 是从人类多能干细胞（hPSC）中产生的，以修复受损的小肠。我们假设 HIO 的细胞复杂性将使其能够维持贯穿壁的移植。为了验证这一点，我们开发了一种啮齿动物损伤模型，通过管腔递送，我们证明了碎裂的 HIO 能够在修复后在整个肠道中植入、增殖和持续存在。不仅观察到了黏膜层的恢复，而且在肌肉层和血管内皮中也观察到了显著的整合。进一步的分析描述了在再生区域内持续存在的细胞类型、保留的近端区域化以及新上皮的功能。这些发现表明间充质对肠道损伤修复的治疗重要性。
