Fibrocytes and fibroblasts—Where are we now

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Abstract

Fibroblasts are considered major contributors to the process of fibrogenesis and the progression of matrix deposition and tissue distortion in fibrotic diseases such as Pulmonary Fibrosis. Recent discovery of the fibrocyte, a circulating possible precursor cell to the tissue fibroblast in fibrosis, has raised issues regarding the characterization of fibrocytes with respect to their morphology, growth characteristics in vitro, their biological role in vivo and their potential utility as a biomarker and/ or treatment target in various human diseases. Characterization studies of the fibrocyte continue as does emerging conflicting data concerning the relationship to or with the lung fibroblast. The source of signals that direct the traffic of these cells, as well as their response to therapeutic intervention with newly available drugs, bring new insights to the understanding of this cell type. The identification of exosomes from fibrocytes that can affect resident fibroblast activities suggest mechanisms of their influence on pathogenesis. Moreover, interesting comparisons with other pathologies are emerging involving the influence of circulating mesenchymal precursor cells on tissue responses.

Introduction

The description of fibrocytes in 1994 by Bucala et al. (1994) marks the beginning of an expanding field of discovery about these fibroblast-like cells, derived from the bone marrow and identified as a circulating mesenchymal cell precursor. Since this initial discovery, there have been an increasing number of studies done on the characterization of fibrocytes with respect to their morphology, growth characteristics in vitro, their biological role in vivo and their potential utility as a biomarker and/or treatment target in various human diseases including asthma, fibrosis of lung, liver and kidney, along with systemic fibrosis and atherosclerosis, to name a few.

Section snippets

Characteristics of fibrocytes

Fibrocytes, which originate from bone marrow, bear characteristics of both fibroblasts and monocytes, and hence exhibit a combination of connective tissue cell and myeloid features (Herzog and Bucala, 2010). Fibrocytes express the stem cell marker CD34, the pan-haematopoietic marker CD45, monocyte markers including CD14 and CD11 and produce components of the connective tissue matrix, such as collagen-I, collagen-III and vimentin (Herzog and Bucala, 2010). Mature fibrocytes express markers of

Controversies regarding fibrocytes in IPF

Fibrocytes represent 0.1–0.5% of peripheral blood leukocytes in healthy individuals (Wang et al., 2007; Chesney et al., 1997). In most experimental models, fibrocyte responses are seen in early phases of tissue injury and fibrocytes appear to be an important source of cytokines and type I collagen, during both the inflammatory and repair phase of the wound healing response, although there remain some controversies regarding this (Chesney et al., 1998; Kleaveland et al., 2014; Bianchetti et al.,

Fibrocytes and cancer-associated fibroblasts

Fibroblasts are amongst the most common cell type in cancer stroma and contribute to the microenvironment critical to sustaining and possibly “protecting” the tumor. It is interesting to consider some striking similarities between the cells in the fibrotic foci in the lung, noted in IPF, to a similar relationship between a solid tumor and cancer-associated fibroblasts (Kidd et al., 2012). Notably, McAllister et al outlined a pathway of solid tumor formation that involved signalling by the

Fibrocytes and exosomes

An increased number of studies in the last few years in the field of exosomes, nanovesicles of endocytic origin secreted by most cell types, has enabled us to enquire about their importance in relation to fibrocytes. This brings us back to the debate about the role of fibrocytes in collagen production during fibrogenesis. Initially regarded as cellular garbage cans to discard unwanted molecular components, newer evidence shows that exosomes act as mediators of intercellular communication by

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