A “Living Bioreactor” for the Production of Tissue-Engineered Small Intestine

  • Daniel E. Levin
  • Frederic G. Sala
  • Erik R. Barthel
  • Allison L. Speer
  • Xiaogang Hou
  • Yasuhiro Torashima
  • Tracy C. Grikscheit
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1001)

Abstract

Here, we describe the use of a mouse model as a living bioreactor for the generation of tissue-engineered small intestine. Small intestine is harvested from donor mice with subsequent isolation of organoid units (a cluster of mesenchymal and epithelial cells). Some of these organoid units contain pluripotent stem cells with a preserved relationship with the mesenchymal stem cell niche. A preparation of organoid units is seeded onto a biodegradable scaffold and implanted intraperitoneally within the omentum of the host animal. The cells are nourished initially via imbibition until neovascularization occurs. This technique allows the growth of fully differentiated epithelium (composed of Paneth cells, goblet cells, enterocytes and enteroendocrine cells), muscle, nerve, and blood vessels of donor origin. Variations of this technique have been used to generate tissue-engineered stomach, large intestine, and esophagus. The variations include harvest technique, length of digestion, and harvest times.

Key words

Tissue engineering Small intestine Organoid unit Short bowel syndrome Living bioreactor 

Notes

Acknowledgments

This work was supported by grants from the California Institute for Regenerative Medicine (#RN2-00946-1) (TG2-01168) and the Saban Research Institute

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Daniel E. Levin
    • 1
  • Frederic G. Sala
    • 1
  • Erik R. Barthel
    • 1
  • Allison L. Speer
    • 1
  • Xiaogang Hou
    • 1
  • Yasuhiro Torashima
    • 1
  • Tracy C. Grikscheit
    • 1
  1. 1.Division of Pediatric Surgery, Saban Research Institute, Children’s Hospital Los AngelesKeck School of Medicine of the University of Southern CaliforniaLos AngelesUSA

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