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Current Problem:

There are many problems before the small intestine construct become a reality for
treating patients SBS.

  • Harvesting sufficient numbers of viable stem cells before surgery is likely to be difficult.
  • None of the studies have demonstrated the ability to tissue engineer a length of intestine equivalent to the amount dissected to supply the organoid units.
  • the amount of intestine that is engineered is not likely to markedly increase the absorptive capacity of the mucosa.
  • There are difficulties associated with expanding organoid units in vitro, with their fate depend on the environment.

Possible Improvements:

A possible solution to increasing the surface area of the neointestine might be with the administration of trophic peptides to the tissue-engineered intestine. Glucagon-like peptide-2 (GLP-2) is a peptide hormone which controls proliferation rates, the size of crypts and villi, and intestinal mass. The study shows that stimulation of neomucosa with GLP-2 resulted in an increase in villus height, crypt cell proliferation index, together with a reduction in apoptosis in the epithelium.

Other approaches to increasing the functional capacity of the tissue-engineered intestine might include gene therapy. Intestinal epithelial stem cells within the units prior to seeding would be an ideal target for gene therapy due to their abundance and location . For example, the transplantation of genetically altered intestinal stem cells would increase the functional capacity.