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Neoplasia and cell/molecular biology free papers 124–139

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124 BONE MARROW DERIVATION OF PERICRYPTAL MYOFIBROBLASTS IN THE MOUSE AND HUMAN SMALL INTESTINE AND COLON

S.J. Forbes1,2, T. Hunt1, M. Brittan1, R. Jeffery1, R. Poulsom1, K. Hodivala-Dilke1, M.R. Alison1,3 , N.A. Wright1,4. 1Histopathology Unit, Imperial Cancer Research Fund, London; 2Department of Medicine, and 3Department of Histopathology, Imperial College School of Medicine; 4Department of Histopathology, Barts and the London, Queen Mary's School of Medicine and Dentistry, London, UK

Background: The intestinal sub-epithelial myofibroblasts (ISEMF) are found in the lamina propria of the intestine under the epithelial cells, and are of critical importance in epithelial-mesenchymal interactions. It has been suggested that the origin of ISEMF might be from the neural crest, or locally from mesenchymal stem cells sited in the muscularis mucosae.

Aims/Methods: In order to establish whether extra-intestinal cells contribute to the turnover and repair of gastrointestinal tissues we studied: (i) the colons and small intestines of female mice that had received whole body irradiation followed by a male bone marrow transplant, (ii) gastrointestinal biopsies from female patients that had received a male bone marrow transplant and then developed graft versus host disease. In situ hybridisation for the Y-chromosomes was combined with immunohistochemistry to define the phenotype of these cells of donor (bone marrow) origin.

Results: In female mouse recipients of male bone marrow grafts we observed clusters of Y-chromosomes positive/ alpha-smooth muscle actin positive myofibroblasts. While few of these were present at 7 days after bone marrow transplantation, they were numerous at 14 days and by 6 weeks, whole columns of pericryptal myofibroblasts could be seen surrounding crypts in both the small intestine and colon. These columns appeared to extend into the villi in the small intestine. In the human intestine we confirmed that the bone marrow-derived cells within the intestine exhibited a myofibroblast phenotype.

Conclusion: …

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