Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts

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 and Harald C. Ott ()
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Kentaro Kitano: Harvard Medical School
Dana M. Schwartz: Harvard Medical School
Haiyang Zhou: Harvard Medical School
Sarah E. Gilpin: Harvard Medical School
Gregory R. Wojtkiewicz: Richard B. Simches Research Center
Xi Ren: Harvard Medical School
Cesar A. Sommer: Boston University School of Medicine
Amalia V. Capilla: Boston University School of Medicine
Douglas J. Mathisen: Harvard Medical School
Allan M. Goldstein: Harvard Medical School
Gustavo Mostoslavsky: Boston University School of Medicine
Harald C. Ott: Harvard Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00779-y

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