King Alice, Balaji Swathi, Le Louis D, Crombleholme Timothy M, Keswani Sundeep G
Laboratory for Regenerative Wound Healing, Division of Pediatric, General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Center for Children's Surgery, Children's Hospital Colorado and the University of Colorado School of Medicine , Aurora, Colorado.
Adv Wound Care (New Rochelle). 2014 Apr 1;3(4):315-323. doi: 10.1089/wound.2013.0461.
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. 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. 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. Further studies on the delivery, including dose, route, and timing, are required in order to successfully translate these promising findings from studies and animal models into clinical practice. IL-10 holds significant potential as an anti-scarring therapeutic.
产后伤口愈合会形成典型的瘢痕。相比之下,妊娠中期的胎儿能够进行再生性愈合,其伤口修复后与未受伤的皮肤无异。然而,胎儿再生表型的潜在机制尚不清楚。强效抗炎细胞因子白细胞介素-10(IL-10)在胎儿再生性愈合能力中起着至关重要的作用,并且已被证明能在产后组织中重现无瘢痕愈合。IL-10促进再生性愈合的能力可能是其多效性作用的结果,它通过调节炎症反应发挥作用,同时还作为细胞外基质、成纤维细胞功能和内皮祖细胞的调节剂发挥新的作用。使用多种方法过表达IL-10已被证明能在产后组织中重现胎儿再生表型,同时使用重组IL-10的II期临床试验也取得了有前景的结果。成功的伤口愈合是一个复杂的过程,需要多种生长因子、细胞类型和细胞外细胞基质成分的协调。IL-10已被证明对胎儿无瘢痕愈合的内在能力至关重要,此外,它还能在产后组织中诱导无瘢痕愈合。IL-10促进这种再生的机制可能是其多效性作用的结果。将IL-10开发为抗瘢痕药物的努力已取得了有前景的结果。为了将这些来自研究和动物模型的有前景的发现成功转化为临床实践,需要对其给药方式进行进一步研究,包括剂量、途径和时机。IL-10作为一种抗瘢痕治疗药物具有巨大的潜力。