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.

Details

Title
Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts
Author
Kitano, Kentaro 1 ; Schwartz, Dana M 1 ; Zhou, Haiyang 2 ; Gilpin, Sarah E 1   VIAFID ORCID Logo  ; Wojtkiewicz, Gregory R 3   VIAFID ORCID Logo  ; Ren, Xi 1 ; Sommer, Cesar A 4 ; Capilla, Amalia V 4 ; Mathisen, Douglas J 5 ; Goldstein, Allan M 6 ; Mostoslavsky, Gustavo 7 ; Ott, Harald C 8 

1  Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 
2  Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China 
3  Center for Systems Biology, Massachusetts General Hospital, Richard B. Simches Research Center, Boston, MA, USA 
4  Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, USA 
5  Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 
6  Division of Pediatric Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 
7  Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, USA; Section of Gastroenterology, Department of Medicine, Boston Medical Center, Boston, MA, USA 
8  Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA 
Pages
1-13
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-00779-y
ProQuest document ID
1949581683
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.