4.3 Article

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

Journal

REGENERATIVE MEDICINE
Volume 11, Issue 1, Pages 45-61

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/rme.15.70

Keywords

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

Funding

  1. Hartwell Biomedical Collaborative Research Award
  2. [R01GM078238]
  3. [RO1DK08752]
  4. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK083752, P30DK089502] Funding Source: NIH RePORTER
  5. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM078238] Funding Source: NIH RePORTER
  6. OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP2OD007155] Funding Source: NIH RePORTER

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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.

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