Leavitt Tripp, Hu Michael S, Marshall Clement D, Barnes Leandra A, Lorenz H Peter, Longaker Michael T
Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA 94305-5461, USA.
Boston University School of Medicine, Boston, MA, USA.
Cell Tissue Res. 2016 Sep;365(3):483-93. doi: 10.1007/s00441-016-2424-8. Epub 2016 Jun 2.
From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal adhesion kinase).
从我们出生的那一刻起，皮肤的每一次损伤都有可能形成疤痕，其中许多疤痕会损害外形和/或功能。因此，疤痕管理构成了一个价值数十亿美元的产业。然而，有效促进无疤痕伤口愈合仍然是一个难以实现的目标。伤口愈合的复杂相互作用导致我们无法重现自然发生的无疤痕伤口修复过程，比如胎儿皮肤和口腔黏膜中的修复过程。不过，近年来已经取得了许多新进展，其中一些已将科学发现从实验室转化到了临床应用。体内谱系追踪有助于确定多种可能作为纤维化反应关键驱动因素的新型细胞罪魁祸首。这些新鉴定出的细胞群体为治疗干预提供了更多靶点，其中一些靶点在动物模型中已显示出有前景的结果。在这里，我们讨论了几项最近的研究，这些研究确定了减少疤痕形成的令人兴奋的方法。我们还将特别关注经典的Wnt/β-连环蛋白信号通路，该通路在胚胎发育和组织修复中都起着重要作用。对Wnt信号在皮肤内异质成纤维细胞和角质形成细胞群体上的不同作用的新见解，进一步证明了可以通过哪些方法将伤口愈合重新导向更接近胎儿的无疤痕表型。图形摘要 减少疤痕形成的最新方法。该图展示了减少疤痕形成的新科学方法，包括基于表面分子表达靶向促纤维化细胞群体（例如二肽基肽酶4阳性成纤维细胞、解整合素金属蛋白酶12阳性周细胞）。调节细胞机械转导途径是另一种减少疤痕形成的方法，无论是在分子水平上，还是在皮肤伤口部位通过设计用于减轻张力的敷料进行宏观调节（解整合素金属蛋白酶12、二肽基肽酶4、粘着斑激酶）
