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Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function.

Christa N Grant1, Salvador Garcia Mojica2, Frederic G Sala2

  • 1Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California; Division of Pediatric Surgery, Children's Hospital Los Angeles, USC Keck School of Medicine, Los Angeles, California;

American Journal of Physiology. Gastrointestinal and Liver Physiology
|January 10, 2015
PubMed
Summary
This summary is machine-generated.

Tissue-engineered small intestine (TESI) shows functional promise for treating short bowel syndrome (SBS). TESI derived from mouse or human cells successfully replicated native intestinal structure and function in vivo.

Keywords:
intestinal failureintestinal stem cellregenerative medicineshort bowel syndrometissue engineering

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Area of Science:

  • Regenerative Medicine
  • Gastroenterology
  • Biotechnology

Background:

  • Short bowel syndrome (SBS) is a severe condition causing malnutrition due to insufficient small intestine surface area.
  • Current treatments like intestinal transplantation face challenges including donor scarcity and lifelong immunosuppression.
  • Tissue-engineered small intestine (TESI) presents a potential alternative therapy.

Purpose of the Study:

  • To investigate whether TESI recapitulates the functional characteristics of native small intestine.
  • To assess the functional integrity of TESI generated from mouse and human cells.

Main Methods:

  • Organoid units were generated from mouse or human donor intestine.
  • TESI units were implanted into genetically identical or immunodeficient host mice.
  • Harvested TESI underwent histological and functional assays after 4 weeks.

Main Results:

  • Both mouse and human TESI formed polarized spheres with intact epithelium, lumen, mesenchyme, muscle, and stem/progenitor cells.
  • The epithelium exhibited key ultrastructural components like tight junctions and microvilli.
  • Functional assays confirmed the presence of transporters, functional brush-border enzymes, and digestive enzymes.

Conclusions:

  • Tissue-engineered small intestine demonstrates a well-differentiated epithelium with functional ion transporters and brush-border enzymes.
  • TESI successfully replicates crucial ultrastructural and functional components of native small intestine.
  • These findings support TESI as a viable therapeutic strategy for short bowel syndrome.