In Vivo Characterization of Bone Marrow–Derived Fibroblasts Recruited into Fibrotic Lesions

Abstract

Fibroblasts, which are widely distributed and play a key part in tissue fibrosis, are phenotypically and functionally heterogeneous. Recent studies reported that bone marrow can be a source of tissue fibroblast. In the study reported here, we investigated in vivo characterization of bone marrowderived fibroblasts recruited into various fibrotic lesions. Mice were engrafted with bone marrow isolated from transgenic mice expressing green fluorescent protein (GFP), and fibrotic lesions were induced by cancer implantation (skin), excisional wounding (skin), and bleomycin administration (lung). A small population of GFP + fibroblast was found even in nonfibrotic skin (8.7% ± 4.6%) and lung (8.9% ± 2.5%). The proportion of GFP + fibroblasts was significantly increased after cancer implantation (59.7% ± 16.3%) and excisional wounding (32.2% ± 4.8%), whereas it was not elevated after bleomycin administration (7.1% ± 2.4%). Almost all GFP + fibroblasts in fibrotic lesions expressed type I collagen, suggesting that bone marrow-derived fibroblasts would contribute to tissue fibrosis. GFP + fibroblasts expressed CD45, Thy-1, and α-smooth muscle actin at various proportions. Our results suggested that bone marrow-derived fibroblasts expressed several fibroblastic markers in vivo and could be efficiently recruited into fibrotic lesions in response to injurious stimuli; however, the degree of recruitment frequency might depend on the tissue microenvironment. Stem Cells 2005;23:699-706

The pathology of tumor stromatogenesis

“…Although the fibroblasts of the host tissue are the most obvious source of the newly formed tumor-associated stroma, recruitment of mesenchymal precursors from bone marrow cannot be excluded. 69,70 It is also probable that transforming growth factor beta 1 (TGFb1) plays a major role in the differentiation of resting fibroblasts to myofibroblasts. 71,72 Cancer cells produce large amounts of TGFb1, especially at the invading tumor front where they interact with fibroblasts of the host organ.…”

PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

“…These data provide unique insight into how skin grafts facilitate tissue repair and identify strategies germane to regenerative medicine for skin and, perhaps, other ectodermal defects or diseases. In skin, studies have shown that BM provides fibroblast-like cells in the dermis (of hematopoietic and mesenchymal lineages) and that the number of these cells increases after skin wounding (3,4). BM can also generate epithelial cells, i.e., keratinocytes, in the epithelia, although the precise derivations and mechanisms to raise BM-derived keratinocytes are not fully known (3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Triiodotironina não aumenta a diferenciação osteogênica reduzida pela idade de células-tronco mesenquimais da medula óssea de ratas

“…A caracterização fenotípica das células antes da diferenciação é fundamental para informar sobre o grau de pureza da cultura, pois a medula óssea pode apresentar CTM, células hematopoéticas (2,29) e fibroblastos (30). As células hematopoéticas expressam, entre outras moléculas, CD45 (2,31) que também pode ser expressa em fibroblastos (30).…”

“…As células hematopoéticas expressam, entre outras moléculas, CD45 (2,31) que também pode ser expressa em fibroblastos (30). A molécula CD73 pode ser expressa tanto em fibroblastos (2) quanto em CTM (30).…”

“…As células hematopoéticas expressam, entre outras moléculas, CD45 (2,31) que também pode ser expressa em fibroblastos (30). A molécula CD73 pode ser expressa tanto em fibroblastos (2) quanto em CTM (30). Mas as moléculas CD90 e CD54 expressas em mais de 86% das células deste estudo são expressas nas CTM, não sendo expressas em fibroblastos e em células hematopoéticas (2,32,33).…”