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Volume 128, Issue 7, Pages (June 2005)

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Presentation on theme: "Volume 128, Issue 7, Pages (June 2005)"— Presentation transcript:

1 Volume 128, Issue 7, Pages 1984-1995 (June 2005)
A Regenerative Role for Bone Marrow Following Experimental Colitis: Contribution to Neovasculogenesis and Myofibroblasts  Mairi Brittan, Victoria Chance, George Elia, Richard Poulsom, Malcolm R. Alison, Thomas T. MacDonald, Nicholas A. Wright  Gastroenterology  Volume 128, Issue 7, Pages (June 2005) DOI: /j.gastro Copyright © 2005 American Gastroenterological Association Terms and Conditions

2 Figure 1 Morphologic characteristics of TNBS-induced colitis. H&E-stained paraffin sections of colons at different time points following administration of ethanol or TNBS, demonstrating the progression of TNBS-induced colitis in irradiated, BM reconstituted mice. (A) Four days after administration of ethanol, crypts appear to have a normal morphology. (B) One day after administration of TNBS, colons are relatively normal with some increased inflammation (inf). (C and D) Eight days after administration of TNBS, colitis is most severe, showing inflammatory cell infiltration (inf), mucosal ulceration (u), fibrosis (f), epithelial cell necrosis, and loss of colonic crypts (n). (E) By day 14 after administration of TNBS, the tissue has almost entirely regenerated and displays a normal morphology. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions

3 Figure 2 BM-derived myofibroblasts in TNBS-induced colitis. BM-derived myofibroblasts were identified by morphologic criteria (ie, spindle-shaped cells in the lamina propria surrounding epithelial crypts) and by their immunoreactivity for both α-SMA (red cytoplasm) and the Y chromosome (dark brown nuclear spot). These cells were frequently identified at all time points in both (A) ethanol-treated controls (4 days after administration of ethanol, arrow) and (B and C) TNBS-treated mice (noninflamed mucosa adjacent to colitis 8 days after administration of TNBS, arrows). BM-derived myofibroblasts were often present as cellular columns spanning from the epithelial crypt base to the intestinal lumen (D: 6 days after administration of ethanol; E and F [inset]: 6 days after administration of TNBS, arrows). (G) Activated myofibroblasts in colitis were identified by their location in regions of fibrosis and by their large, flat shape (6 days after administration of TNBS, arrows). (H and I [inset]) BM-derived activated myofibroblasts were present in the submucosa in regions of regenerating epithelium (8 days after administration of TNBS, arrows). n, necrotic epithelial crypts; u, mucosal ulcer; f, fibrosis; re, epithelialization. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions

4 Figure 3 BM contributes to multiple vascular lineages and can form entire blood vessels in TNBS-induced colitis. BM-derived VSMCs were identified as smooth muscle-like cells surrounding the blood vessels that were SMA immunoreactive and possessed the Y chromosome (dark brown nuclear spot). (A and high-power inset [B–D]) BM-derived VSMCs were frequently interspersed throughout blood vessels in inflamed colons (6 days after administration of TNBS, arrows). (E and F) Additionally, the role of BM in postnatal vasculogenesis was confirmed by the presence of whole blood vessels composed entirely of BM-derived cells (arrows). (G) In grossly inflamed regions, the tissue was highly vascularized with small, leaky vessels and BM-derived pericytes were frequently present in these structures (8 days after administration of TNBS, arrows). BM-derived endothelial cells were identified as cells that were ICAM-1 immunoreactive (red cytoplasm) and possessed a Y chromosome (dark brown nuclear spot). (H and I) These cells were also observed in inflamed regions in colitis (8 days after administration of TNBS, arrows). Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions

5 Figure 4 BM-derived intestinal and vascular lineages do not express hematopoietic and macrophage markers. Blood vessels in inflamed colons contained cells that displayed a Y chromosome (dark brown nuclear spot) but did not express (A, B, and D) the macrophage marker F4/80 (6 days after administration of TNBS, arrows) or (E and F) the hematopoietic marker CD34 (8 days after administration of TNBS, arrows). (C) BM-derived cells in the lamina propria that were morphologically typical of myofibroblasts lacked expression of F4/80 (6 days after administration of TNBS, arrows in high-power inset). Macrophages or hematopoietic cells derived from the BM, that is, cells with a nuclear Y chromosome that were immunoreactive for F4/80 (A–D, asterisk) or (E and F, asterisk) CD34, respectively, provided an internal control for these experiments. (B) Some cells lacked expression of F4/80 and expressed a Y chromosome but were not believed to be either VSMCs or endothelial cells due to their morphology and location (arrowheads). Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions


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