Regenerative Wound Healing: The Role of Interleukin-10.
Significance:Postnatal wounds heal with characteristic scar formation. In contrast, the mid-gestational fetus is capable of regenerative healing, which results in wound repair that is indistinguishable from uninjured skin. However, the underlying mechanisms of fetal regenerative phenotype are unknown.Recent Advances:The potent anti-inflammatory cytokine, interleukin-10 (IL-10), plays an essential role in the ability of the fetus to heal regeneratively and has been shown to recapitulate scarless healing in postnatal tissue. IL-10's ability to facilitate regenerative healing is likely a result of pleiotropic effects, through regulation of the inflammatory response, as well as novel roles as a regulator of the extracellular matrix, fibroblast cellular function, and endothelial progenitor cells. Overexpression of IL-10 using a variety of methods has been demonstrated to recapitulate the fetal regenerative phenotype in post-natal tissue, in conjunction with promising results of Phase II clinical trials using recombinant IL-10.Critical Issues:Successful wound healing is a complex process that requires coordination of multiple growth factors, cell types, and extracellular cellular matrix components. IL-10 has been demonstrated to be critical in the fetus' intrinsic ability to heal without scars, and, further, can induce scarless healing in postnatal tissue. The mechanisms through which IL-10 facilitates this regeneration are likely the result of IL-10's pleiotropic effects. Efforts to develop IL-10 as an anti-scarring agent have demonstrated promising results.Future Directions:Further studies on the delivery, including dose, route, and timing, are required in order to successfully translate these promising findings fromin vitrostudies and animal models into clinical practice. IL-10 holds significant potential as an anti-scarring therapeutic.
Laboratory for Regenerative Wound Healing, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Alice
A
King
Laboratory for Regenerative Wound Healing, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Swathi
S
Balaji
Laboratory for Regenerative Wound Healing, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Louis D
LD
Le
Center for Children's Surgery, Children's Hospital Colorado and the University of Colorado School of Medicine , Aurora, Colorado.
Timothy M
TM
Crombleholme
Laboratory for Regenerative Wound Healing, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Sundeep G
SG
Keswani