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

Author

Listed:
  • Kentaro Kitano

    (Harvard Medical School)

  • Dana M. Schwartz

    (Harvard Medical School)

  • Haiyang Zhou

    (Harvard Medical School
    Second Military Medical University)

  • 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
    Boston Medical Center)

  • Harald C. Ott

    (Harvard Medical School
    Harvard Stem Cell Institute)

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.

Suggested Citation

  • 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 Mostosla, 2017. "Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00779-y
    DOI: 10.1038/s41467-017-00779-y
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