Direkze, N.C.; Forbes, S.; Brittan, M.; Hunt, T.; Jeffery, R.; Preston, S.L.; Poulson, R.; Hodivala-Dilke, K.; Alison, M.; Wright, N.A.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA50
Academic Journal
Background: Our previous work has shown that bone marrow can make important contributions to the myofibroblast population in the lamina propria after bone marrow transplantation (Gut 2002;50:752-7). Here we show that the bone marrow can also contribute to fibroblast populations in sites of injury, and in fact, the engraftment of cells destined to be myofibroblasts from the bone marrow appears to be a systemic phenomenon not confined to gastrointestinal tissues. Methods: C57/black female mice were irradiated with a total of 12 Gray to ablate the bone marrow followed immediately by I.V. injection of male wild type whole bone marrow. The mice received 2 doses of paracetamol at 5 and 8 weeks post transplantation at a dose of 400mg/kg I.P. Tissue sections were examined using in situ hybridisation to detect the Y-chromosome and immunohistochemistry for intermediate filaments and cytoskeletal elements. Results: Examination of the intestine and stomach showed numerous myofibroblasts of bone marrow origin distributed throughout the gut wall. In addition, areas of fibrosis contained numerous Y chromosome positive cells with a fibroblastic phenotype. Myofibroblast engraftment was also demonstrated in the skin, adrenal capsule, lung, and kidney. Conclusions: We conclude that bone marrow provides a circulating population of cells which can contribute to myofibroblasts in healing tissues. Our data also suggest that these cells can adopt a fibroblastic phenotype and contribute to fibrosis. We therefore hypothesise that circulating bone marrow-derived precursors are available which are able to colonise injured tissues and give rise to myofibroblasts and then fibroblasts. These conclusions have important connotations for tissue repair in gastrointestinal and other tissues.


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