In Vivo Regeneration of Tubular Small Intestine With Motility: A Novel Approach by Orthotopic Transplantation of Decellularized Scaffold

去细胞化 移植 小肠 肠神经系统 病理 再生(生物学) 脚手架 医学 组织工程 解剖 生物医学工程 生物 外科 内科学 细胞生物学
作者
Hidenobu Kojima,Takamichi Ishii,Ken Fukumitsu,Satoshi Ogiso,Akio Saiura,Yu Oshima,Hiroshi Horie,Takashi Ito,Satoshi Wakama,Kenta Makino,Etsuro Hatano
出处
期刊:Transplantation [Ovid Technologies (Wolters Kluwer)]
卷期号:107 (9): 1955-1964 被引量:3
标识
DOI:10.1097/tp.0000000000004522
摘要

Background. 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. Methods. 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. Results. 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. Conclusions. 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.

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