Peripheral Blood Fibrocytes Enhancement of Wound Healing by Cell Proliferation, Re-Epithelialization, Contraction, and Angiogenesis

Objective: To identify the in vitro characteristics and functional properties of fibrocytes and investigate the in vivo mechanism of action of fibrocytes injection in accelerating the cutaneous healing process in diabetic mice. Background: Fibrocytes are hematopoietic derived stem cells that may have a role in tissue repair, perhaps as the precursors of fibroblast-or myofibroblast-like cells. Methods: In vitro, the time-dependent phenotypic expression of peripheral blood (PB) fibrocytes was stained with anti-CD11b, anti-CD45, anti-Col-I, and anti-alpha-SMA antibodies. The functional properties of fibrocytes and dermal fibroblasts were tested by using reverse-transcriptase polymerase chain reaction. In vivo, full thickness wounds in diabetic mice were treated either with fibrocytes, dermal fibroblasts, or phosphate buffered saline (PBS) through tail vein injection. Wound healing kinetics, including wound contraction, re-epithelialization, and microscopic metrics such as cell proliferation, angiogenesis, and granulation growth were investigated. Expression of proinflammatory factors, profibrotic factors, growth factors, and extracellular matrix components were measured in wound tissues. Results: Fibrocytes gradually lose their hematopoietic cell markers and increase mesenchymal cell markers during differentiation in vitro. Fibrocytes stimulate wound healing by dermal cell proliferation, keratinocyte proliferation with re-epithelialization, and angiogenesis compared with dermal fibroblast and PBS treated wounds. Expression of angiogenesis markers (VEGF and b-FGF), growth factors (TGF-beta, PDGF-A, and FGF-7), chemokines (MCP-1 and MIP-1 alpha), and extracellular matrix (collagen-I and alpha-SMA) were upregulated in fibrocyte-treated wounds. Conclusion: Peripheral blood fibrocytes can accelerate wound healing by stimulating cell proliferation, re-epithelialization, and angiogenesis in a diabetic mice experimental model. The application of fibrocytes may represent a potential clinical solution for the treatment of chronic wounds across all fields of surgery.