当前位置：文档之家 > The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and MINI REVIEWThe role of the fibrocyte,a bone marrow-derived mesenchymal progenitor,in reactive and reparative fibrosesAlberto Bellini and Sabrina MattoliHuman fibrocytes are mesenchymal progenitors that exhibit mixed morphological and molecular characteristics of hematopoietic stem cells,monocytes and fibroblasts.They likely represent the obligate intermediate stage of differ-entiation into mature mesenchymal cells of a bone marrow-derived precursor of the monocyte lineage under permissive conditions.On in vitro stimulation with pro-fibrotic cytokines and growth factors,human fibrocytes produce large quantities of extracellular matrix components and further differentiate into cells identical to the contractile myofibro-blasts that emerge at the tissue sites during repair processes and in some fibrotic lesions.Studies in various animal models of wound healing or fibrotic diseases have confirmed the ability of fibrocytes to differentiate into mature mesenchymal cells in vivo and have suggested a causal link between fibrocyte accumulation and ongoing tissue fi-brogenesis or vascular remodeling in response to tissue damage or hypoxia.Fibrocytes synthesizing new collagen or acquiring myofibroblast markers have been detected in human hypertrophic scars,in the skin of patients affected by nephrogenic systemic fibrosis,in human atherosclerotic lesions,and in pulmonary diseases characterized by repeated cycles of inflammation and repair,like asthma.The presence of fibrocyte-like cells has been reported in human chronic pancreatitis and chronic cystitis.Similar cells also populate the stroma surrounding human benign tumors.The available data indicate that human fibrocytes serve as a source of mature mesenchymal cells during reparative processes and in fibrotic disorders or stromal reactions predominantly associated with a persistent inflammatory infiltrate or with the selective recruitment of monocytes induced by ischemic changes and tumor development.A deeper understanding of the mechanisms involved in fibrocyte differentiation in these pathological conditions may lead to the development of novel therapies for preventing detrimental tissue or vascular remodeling and metastatic progression of invasive tumors.Laboratory Investigation (2007)87,858–870;doi:10.1038/labinvest.3700654;published online 2July 2007KEYWORDS:asthma;atherosclerosis;fibrocytes;myofibroblasts;tissue repair;tumorThe fibrocytes 1–5are bone marrow-derived mesenchymal progenitors 6–9that coexpress hematopoietic stem cell anti-gens,markers of the monocyte lineage and fibroblast products.1–6,10,11They constitutively produce extracellular matrix (ECM)components as well as ECM-modifying enzymes,1–3,5,11and can further differentiate into myofibro-blasts both in vitro and in vivo under permissive micro-en-vironmental conditions.3,5,10,11There is increasing evidence that these cells contribute to the new population of fibro-blasts and myofibroblasts that emerge at the tissue site during normal 1,3,6or aberrant 12wound healing,in ischemic or inflammatory fibrotic processes,8,9,11,13–24and as part of the stromal reaction to tumor development.13,24–32This review will focus on the origin of human fibrocytes and theirinvolvement in the pathogenesis of reactive and reparative fibroses in human diseases.HEMATOPOIETIC ORIGIN AND MESENCHYMAL PROPERTIES OF HUMAN FIBROCYTES Origin and Phenotypic CharacteristicsThe term fibrocyte was first used in 1994to define a sub-population of leukocytes that accumulate at sites of tissue injury and show fibroblast properties.1In the initial report,fibrocytes were found to express the hematopoietic stem cell/progenitor marker CD34,the leukocyte common antigen CD45(a pan-hematopoietic marker)and several markers of the monocyte lineage in conjunction with vimentin and collagens.1The phenotypic characteristics of these cells wereReceived 24April 2007;revised 2June 2007;accepted 3June 2007Avail Biomedical Research Institute,Basel,SwitzerlandCorrespondence:Dr S Mattoli,MD,PhD,Avail Biomedical Research Institute,PO Box 110,Basel CH-4003,Switzerland.E-mail:smattoli@http://www.doczj.com/doc/2803299951e79b8968022670.html Laboratory Investigation (2007)87,858–870&2007USCAP,Inc All rights reserved 0023-6837/07$30.00上一页下一页