Fibrocytes and Other Fibroblast/Myofibroblast Progenitors in Systemic Sclerosis

Systemic sclerosis (SSc), also called scleroderma, is a fibrosing autoimmune disease. There are several different clinical types of SSc that have variable internal organ fibrosis and degrees of skin involvement with fibrosis. A prominent vasculopathy often precedes the onset of fibrosis. The origins of myofibroblasts which are the dominant matrix synthesizing cell in SSc involved tissue has traditionally been thought to arise from transformation of resident fibroblasts left over from embryonic development in response to cytokine/growth factor stimulation from activated T cells and monocytes that populate areas of fibrosis in SSc organs. We have evidence that the blood mononuclear cells generate large numbers of fibroblast-like cells when they are cultured with an auto antigen for SSc, type I collagen. Development of myofibroblasts from epithelial mesenchymal transition (EMT), pericytes and fibrocytes are discussed as possible contributors to fibrosis in SSc. Implication of alternative sources of myofibroblasts in SSc from the traditionally held view of their development from resident fibroblasts for therapeutic approaches is discussed.