Bioengineering of Functional Human Induced Pluripotent Stem Cell-derived Intestinal Grafts

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Oct 12

PMID 29018244

Citations 48

Authors

Kentaro Kitano

Dana M Schwartz

Haiyang Zhou

Sarah E Gilpin

Gregory R Wojtkiewicz

Xi Ren

Cesar A Sommer

Amalia V Capilla

Douglas J Mathisen

Allan M Goldstein

Gustavo Mostoslavsky

Harald C Ott

Affiliations

Soon will be listed here.

Abstract

Patients with short bowel syndrome lack sufficient functional intestine to sustain themselves with enteral intake alone. Transplantable vascularized bioengineered intestine could restore nutrient absorption. Here we report the engineering of humanized intestinal grafts by repopulating decellularized rat intestinal matrix with human induced pluripotent stem cell-derived intestinal epithelium and human endothelium. After 28 days of in vitro culture, hiPSC-derived progenitor cells differentiate into a monolayer of polarized intestinal epithelium. Human endothelial cells seeded via native vasculature restore perfusability. Ex vivo isolated perfusion testing confirms transfer of glucose and medium-chain fatty acids from lumen to venous effluent. Four weeks after transplantation to RNU rats, grafts show survival and maturation of regenerated epithelium. Systemic venous sampling and positron emission tomography confirm uptake of glucose and fatty acids in vivo. Bioengineering intestine on vascularized native scaffolds could bridge the gap between cell/tissue-scale regeneration and whole organ-scale technology needed to treat intestinal failure patients.There is a need for humanised grafts to treat patients with intestinal failure. Here, the authors generate intestinal grafts by recellularizing native intestinal matrix with human induced pluripotent stem cell-derived epithelium and human endothelium, and show nutrient absorption after transplantation in rats.

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