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RITS study: Regenerating Intestinal Tissue with Stem cells, transplantation of adult human intestinal stem cells as an alternative to organ transplantation

Friday 18 February 2011

Project
The intestinal epithelium is the most rapidly self-renewing tissue in mammals. Recently, Hans Clevers and co-workers (Hubrecht institute) have shown the presence of cycling stem cells that reside at the bottom of intestinal crypts. Upon differentiation, cells migrate along the crypt-villus axis towards to tip of the villus. It has been shown that the stemcells constitute multipotent cells that generate all cell types of the epithelium. However, the transplantation potential of the stem cells in vivo is still undetermined.

The potential of intestinal stem cells to renew intestinal tissue in case of epithelial damage will be instrumental for the applicability of transplantation in human disease. One example of human disease that qualifies for tissue-specific stem cell transplantation is the autosomal recessive microvillus inclusion disease (MVID) that is characterized by an intractable diarrhea starting within the first few weeks of life. The hallmarks of MVID are a lack of microvilli on the surface of villous enterocytes, occurrence of intracellular vacuoles lined by microvilli, microvillus inclusions. These patients are completely dependent on parenteral feeding and require intestinal transplantation in order to survive. Organ transplantation is a treatment with many drawbacks and may not be sufficient for survival. When intestinal stem cells from a matched donor are able to renew intestinal tissue, these patients have a better chance of survival.

We can determine the transplantation potential of stem cells by using engineered intestinal tissue (organoids) from LacZ-expressing mice. These mice show blue stemcells when stained for LacZ.. LacZ+ donor stem cells can be traced in intestines of LacZ-negative recipient mice. When LacZ+ cells are detected in the intestines of recipient mice, we have proven the transplantation potential and specific (immuno)histological stainings will show us wheather the transplanted tissue is fully functional.

The RITS study involves pre-clinical and clinical research in order to utilize the engineered intestinal tissue for future clinical interventions.

Techniques
Cell culture of T cells and different types of DC, FACS, Elisa, luminex, gel electrophoresis, confocal microscopy, immunohistochemistry, in vivo animal studies

Duration
6 or 9 months

Contact
Dr. Mark Klein, 088 75 555 55 (pager 4118), mklein01@umcutrecht.nl

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