Stem Cells in Dermal Wound Healing

Abstract

Repair of damaged dermal tissue is accomplished by dynamic cell-cell and cell-matrix interactions involving activation of resident cells as well as cells that migrate into the lesion. Immediately after injury there is a hemostatic response that activates platelets. Platelets release transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), which begin the recruitment of inflammatory cells and activate several resident dermal cell types. The most notable early inflammatory response is the infiltration of neutrophils. These are necessary to control infection and begin clearing the damaged tissue but are not critical to the healing process. Wound healing begins a few days later with the infiltration of monocyte/macrophages at the site. These cells release a number of cyotokines, synthesize extracellular matrix (ECM), and serve as a source of stem cells. The ECM becomes vascularized by angiogenesis and forms granulation tissue. Neovascularization is accomplished using both resident endothelial cells and circulating progenitor cells from the blood. Scar formation proceeds with the activation, migration, and proliferation of fibroblasts and the formation of a three-dimensional scaffold of ECM. A hematologically derived monocyte/stem cell may be the major contributor to early matrix synthesis. These blood-derived stem cells are able to produce a wide variety of proinflammatory cytokines (IL-1β, TNF-α, MIP-1α, MIP-1β, PDGF-A and TGF-β), which make major contributions to the healing process. Contraction of the wound is driven by activation and differentiation of mesenchymal cells into myofibroblasts that are able to draw the edges of the damaged tissue over the deficit. Migration of viable keratinocytes within the wound and from the edges of it stimulated by types I and IV collagen, fibronectin and vitronectin, as well as serum factors is responsible for reepithelialization of the surface. The cells include both the basal stem cells of the epidermis and the transit-amplifying cells. If epidermal stem cells are lost, migrating stem cells from surviving hair follicles are able to supply epidermal cells.