Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Transplantation. 2023 Sep 1;107(9):1955-1964. doi: 10.1097/TP.0000000000004522. Epub 2023 Aug 21.
Whole-intestine engineering can provide a therapeutic alternative to bowel transplantation. Intestinal components including the mucosa, muscular layer, enteric nervous system, and vasculature must be reestablished as a tubular organ to generate an artificial small intestine. This study proposes a novel approach to produce a transplantable, well-organized tubular small intestine using a decellularized scaffold.
Male Lewis rat intestines were used to generate decellularized scaffolds. Patch or tubular grafts were prepared from the decellularized intestine and transplanted into the rat intestine orthotopically. Histological analysis of the decellularized intestine was performed up to 12 wk after transplantation.
Histological examination revealed abundant vascularization into the decellularized patch graft 1 wk after transplantation. Muscular and nervous components, as well as cryptogenesis, were observed in the decellularized patch graft 2 wk after transplantation. Sixteen of the 18 rats survived with normal intake of food and water after the decellularized tubular graft transplantation. Compared with silicone tube grafts, the decellularized tubular grafts significantly promoted the infiltration and growth of intestinal components including the mucosa, muscular layer, and nerve plexus from the recipients. Circular and longitudinal muscle with a well-developed myenteric plexus was regenerated, and intestinal motility was confirmed in the decellularized tubular graft 12 wk after transplantation.
Orthotopic transplantation of decellularized intestine enhanced the reconstruction of the well-organized tubular small intestine with an enteric nervous system in vivo. Our method using a decellularized scaffold represents a promising approach toward whole-intestine engineering and provides a therapeutic alternative for the irreversible intestinal failure.
全肠工程可以为肠移植提供一种治疗替代方案。肠的组成部分，包括黏膜、肌层、肠神经系统和脉管系统，必须重建为管状器官，以产生人工小肠。本研究提出了一种使用脱细胞支架生产可移植的、组织良好的管状小肠的新方法。
使用雄性 Lewis 大鼠的肠来生成脱细胞支架。从脱细胞肠制备贴片或管状移植物，并将其原位移植到大鼠肠中。在移植后 12 周内对脱细胞肠进行组织学分析。
组织学检查显示，移植后 1 周，脱细胞贴片移植物中大量血管化。移植后 2 周，在脱细胞贴片移植物中观察到肌和神经成分以及隐窝发生。18 只大鼠中有 16 只在脱细胞管状移植物移植后存活，正常摄入食物和水。与硅胶管移植物相比，脱细胞管状移植物显著促进了包括黏膜、肌层和神经丛在内的肠组织从受者中的渗透和生长。在移植后 12 周，再生了具有发达肌间神经丛的环形和纵向肌肉，并确认了脱细胞管状移植物中的肠动力。
脱细胞肠的原位移植增强了体内具有肠神经系统的组织良好的管状小肠的重建。我们使用脱细胞支架的方法代表了一种有前途的全肠工程方法，并为不可逆性肠衰竭提供了一种治疗替代方案。
