A regenerative role for bone marrow following experimental colitis: contribution to neovasculogenesis and myofibroblasts.
OBJECTIVE
Bone marrow (BM) cells form differentiated adult lineages within nonhematopoietic tissues, with a heightened propensity with increasing regenerative pressure dictated by disease. We have previously shown that BM cells engraft into the gut and contribute substantially to the subepithelial intestinal myofibroblast population in the lamina propria. To investigate the reparative capacity of BM in inflammatory bowel disease (IBD), a well-established model of experimental colitis was used.


METHODS
Lethally irradiated female mice were rescued by a BM transplant from male donors. Colitis was induced 6 weeks posttransplantation by injection of trinitrobenzene sulfonic acid (TNBS), and tissues were analyzed 1-14 days later. Donor-derived cells were detected by in situ hybridization using a Y chromosome-specific probe, and their phenotype was determined by immunohistochemistry.


RESULTS
TNBS-induced colitis was manifest as patchy lesions that increased in severity between days 1 and 8, and the mucosa gradually regenerated between days 8 and 14. The contribution of BM to intestinal myofibroblasts was significantly increased in regions of colitis compared with noninflamed regions. Furthermore, BM-derived endothelial cells, pericytes, and vascular smooth muscle cells were frequently interspersed throughout blood vessels, suggesting that these cells facilitate angiogenesis in tissue repair, substantiated by a significant increase in the incidence of BM-derived vascular smooth muscle cells in colitic compared with noninflamed regions. Blood vessels formed entirely from BM-derived cells were also seen, suggesting a role for BM in neovasculogenesis.


CONCLUSIONS
Our data show that BM contributes to multiple intestinal cell lineages in colitis, with an important function in tissue regeneration and vasculogenesis after injury.
Brittan
Mairi
M
Histopathology Unit, Cancer Research UK, London Research Institute, United Kingdom. mairi.brittan@cancer.org.uk
Chance
Victoria
V
Elia
George
G
Poulsom
Richard
R
Alison
Malcolm R
MR
MacDonald
Thomas T
TT
Wright
Nicholas A
NA
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003092:Colitis / Q000503:physiopathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D018919:Neovascularization, Physiologic; D014998:Y Chromosome