Platelet-derived transforming growth factor-beta 1 promotes keratinocyte proliferation in cutaneous wound healing

Platelets are a recognised potent source of transforming growth factor-beta 1 (TGF beta 1), a cytokine known to promote wound healing and regeneration by stimulating dermal fibroblast proliferation and extracellular matrix deposition. Platelet lysate has been advocated as a novel personalised therapeutic to treat persistent wounds, although the precise platelet-derived growth factors responsible for these beneficial effects have not been fully elucidated. The aim of this study was to investigate the specific role of platelet-derived TGF beta 1 in cutaneous wound healing. Using a transgenic mouse with a targeted deletion of TGF beta 1 in megakaryocytes and platelets (TGF beta 1(fl/fl).PF4-Cre), we show for the first time that platelet-derived TGF beta 1 contributes to epidermal and dermal thickening and cellular turnover after excisional skin wounding. In vitro studies demonstrate that human dermal fibroblasts stimulated with platelet lysate containing high levels of platelet-derived TGF beta 1 did not exhibit enhanced collagen deposition or proliferation, suggesting that platelet-derived TGF beta 1 is not a key promoter of these wound healing processes. Interestingly, human keratinocytes displayed enhanced TGF beta 1-driven proliferation in response to platelet lysate, reminiscent of our in vivo findings. In summary, our novel findings define and emphasise an important role of platelet-derived TGF beta 1 in epidermal remodelling and regeneration processes during cutaneous wound healing.