oa The Role of a Human Hematopoietic Mesenchymal Progenitor in Wound Healing and Fibrotic Diseases and Implications for Therapy

The human peripheral blood contains a multipotent precursor that shows hematopoietic stem cell features and transiently expresses markers of the myeloid lineage. Under permissive conditions, this precursor gives rise to committed progenitors of various lineages, including a mesenchymal progenitor cell known by the name of fibrocyte. The fibrocytes still express some hematopoietic and myeloid antigens together with fibroblast markers. They constitutively release profibrotic and angiogenic factors and can modulate ongoing inflammatory reactions through the release of a number of chemokines. Under appropriate stimulation, fibrocytes produce increased amounts of extracellular matrix components and acquire a contractile phenotype similar to that of activated fibroblasts (myofibroblasts). Fibrocytes synthesizing new collagen or acquiring myofibroblast markers have been detected in pulmonary diseases characterized by an extensive remodeling of the bronchial wall or progressive fibrosis, in the skin of patients affected by nephrogenic systemic fibrosis, in human hypertrophic scars, in proliferative vitreoretinopathies and atherosclerotic lesions. Similar cells also participate in the stromal reaction to tumor development. Prevention of detrimental tissue remodeling in fibrotic diseases may be achieved by inhibiting the accumulation of fibrocytes. In-vitro expanded fibrocytes may be used to improve ineffective tissue repair or may be engineered for the delivery of gene constructs in anti-cancer therapy.