The role of the fibrocyte in intimal hyperplasia

Abstract

Summary. Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow-derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. Objectives: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. Methods and results: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha-smooth muscle actin (a-SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and a-SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and a-SMA) and also to double stain for CD34 and a-SMA. Conclusions: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury.

Fibrocytes: potential new therapeutic targets for pulmonary hypertension?

“…Further, one of the subsets of monocytes that are preferentially recruited into the arterial wall during experimentally induced arteriosclerosis in mice represents the murine counterpart of the human inflammatory subset of CD14+/CD16-mononuclear cells that express the CC chemokine ligand (CCL) 2/monocyte chemoattractant protein (MCP)-1 receptor CCR2 [22]. Consistent with findings from the murine models are studies demonstrating that the intimal hyperplasia in an ovine carotid artery patch graft model is partially due to haematopoietic circulating fibrocytes that acquire mesenchymal features as they mature at the site of injury [23]. Other studies demonstrate that fibrocytes or fibrocyte-like cells (CD14+-derived mesenchymal cells) play an important role in the remodelling that characterises transplant vasculopathy [24][25][26][27].…”

Immunohistochemical Characterization of Neotissues and Tissue Reactions to Septal Defect–Occlusion Devices

“…Fibrocytes are circulating cells, which migrate into wounds and adopt a smooth muscle-like phenotype (spindle-shape morphology, positive staining for vimentin, and smooth muscle actin). Varcoe et al 17 demonstrated that these cells are involved in intima formation. It can be assumed that these cells are involved in the organization of the thrombotic material and the formation of the pseudointima, as seen in our collection of specimen.…”

Imatinib ameliorates bronchiolitis obliterans via inhibition of fibrocyte migration and differentiation

“…Previous animal studies suggest that differentiation of fibrocytes from circulating monocytes mainly occurs at tissue sites and not in the peripheral blood (17,44,45). A recent study demonstrated that the monocyte-macrophage axis contributed to the development of chronic graft-versus-host disease, including BO (46).…”