1442 Bone marrow-derived fibrocytes contribute to type I collagen production during the early stage of cutaneous wound repair

Abstract

Substantial induction of type I collagen (COL1) production is essential for regeneration of the dermal extracellular matrix during wound repair. Skin resident fibroblasts are the major cell type responsible for increased COL1. Fibrocytes are circulating bone marrow-derived cells that have the capacity to produce COL1. In tissues, fibrocytes are identified as CD45+ positive (pan hemopoietic marker) cells that express COL1. The involvement of fibrocytes in human wound healing is unclear. We have investigated the presence of fibrocytes in experimental human wounds. Partial thickness wounds were created on the buttock by ablative CO2 laser. Skin samples were obtained at baseline, 1, 3 and 5 weeks post wounding, and analyzed by immunostaining and gene expression. Immunostaining revealed that CD45+ positive cells accounted for the majority of cells, in the upper dermis at 1 week after wounding. Fifteen percent (n=8) of the CD45+ positive cells expressed COL1 protein. These CD45+/COL1+ double positive cells accounted for 26% of total COL1+ positive cells. CD45+/COL1+ double positive cells were not found 3 or 5 weeks post wounding. Consistent with these results, 14% of CD45+ positive cells that were isolated from skin one-week post wounding expressed COL1 mRNA, while no COL1 mRNA was detected in CD45+ positive cells that were isolated 3 or 5 weeks post wounding. Interestingly, fibrocytes cultured from blood or wounded skin rapidly lost CD45 expression and became indistinguishable from primary dermal fibroblasts. The above results indicate that fibrocytes rapidly home to human skin and express approx. 25% of total COL1 in early wounds. Loss of CD45 by fibrocytes may mask their full long-term contribution to wound healing. Limited fibrocyte homing to wounds, due to poor circulation, might account, in part, for weakened wound healing observed in persons with diabetes or the aged. Promoting fibrocyte entry into skin represents a novel therapeutic strategy to improve healing of refractory wounds.