Intestinal stem cell growth and differentiation on a tubular scaffold with evaluation in small and large animals

Regen Med. 2016 Jan;11(1):45-61. doi: 10.2217/rme.15.70. Epub 2015 Sep 23.

Abstract

Aims: To investigate the growth and differentiation of intestinal stem cells on a novel tubular scaffold in vitro and in vivo.

Materials & methods: Intestinal progenitor cells from mice or humans were cultured with myofibroblasts, macrophages and/or bacteria, and evaluated in mice via omental implantation. Mucosal regeneration was evaluated in dogs after rectal mucosectomy followed by scaffold implantation.

Results: Intestinal progenitor cells differentiated into crypt-villi structures on the scaffold. Differentiation and scaffold coverage was enhanced by coculture with myofibroblasts, macrophages and probiotic bacteria, while the implanted scaffolds enhanced mucosal regeneration in the dog rectum.

Conclusion: Intestinal stem cell growth and differentiation on a novel tubular scaffold is enhanced through addition of cellular and microbial components, as validated in mice and dogs.

Keywords: artificial intestine; intestinal stem cells; necrotizing enterocolitis; scaffold; short bowel syndrome; tissue-engineered small intestine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / pathology
  • Cell Differentiation*
  • Cell Proliferation
  • Coculture Techniques
  • Disease Models, Animal
  • Dogs
  • Escherichia coli / physiology
  • Inflammation / pathology
  • Intestine, Small / cytology*
  • Lactic Acid / chemistry
  • Lactobacillus / physiology
  • Mice, Inbred C57BL
  • Microvilli / ultrastructure
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Stem Cell Niche
  • Stem Cell Transplantation
  • Stem Cells / cytology*
  • Tissue Scaffolds / chemistry*

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid