Transplantation of a Human Tissue-Engineered Bowel in an Athymic Rat Model.

Abstract

Intestinal failure is a serious clinical condition characterized by loss of motility, absorptive function, and malnutrition. Current treatments do not provide the optimal solution for patients due to the numerous resulting complications. A bioengineered bowel that contains the necessary cellular components provides a viable option for patients. In this study, human tissue-engineered bowel (hTEB) was developed using a technique, whereby human-sourced smooth muscle cells were aligned and neoinnervated using human-sourced neural progenitor cells, resulting in the formation of intrinsically innervated smooth muscle sheets. The sheets were then rolled around hollow tubular chitosan scaffolds and implanted in the omentum of athymic rats for neovascularization. Four weeks later, biopsies of hTEB showed vascularization, normal cell alignment, phenotype, and function. During the biopsy procedure, hTEB was transplanted into the same rat's native intestine. The rats gained weight and 6 weeks later, hTEB was harvested for studies. hTEB was healthy in color with normal diameter and with digested food in the lumen, indicating propulsion of luminal content through the hTEB. Histological studies indicated neomucosa with evidence of crypts and villi structures. This study provides proof of concept that hTEB could provide a viable treatment to lengthen the gut for patients with gastrointestinal disorders.