Cutting into wound repair

Abstract

The skin is home to an assortment of fibroblastic lineages that shape the wound repair response toward scars or regeneration. In this review, we discuss the distinct embryonic origins, anatomic locations, and functions of fibroblastic lineages, and how these distinct lineages of fibroblasts dictate the skin's wound response across injury depths, anatomic locations, and embryonic development to promote either scarring or regeneration. We highlight the supportive role of the fascia in dictating scarring outcomes; we then discuss recent findings that indicate fascia mobilization by its resident fibroblasts supersede the classical de novo deposition program of wound matrix formation. These recent findings reconfigure our traditional view of wound repair and present exciting new therapeutic avenues to treat scarring and fibrosis across a range of medical settings.

Furnishing Wound Repair by the Subcutaneous Fascia

“…Furthermore, studies by Harris and colleagues showed that the traction force of individual fibroblasts in wounds was significantly more than the force needed for cell movement and hypothesized that the extra force was used for dragging matrix fibers [45]. The recent findings of the pivotal role for subcutaneous fascia support these earlier findings [29,46].…”

“…Superficial fascia is constantly thicker in women compared to men at various anatomical sites. For instance, female subcutaneous fascia at back is 15% thicker than male (0.16 mm vs. 0.14 mm) [13], while back skin in women is 55% thinner than in men (1.5 mm vs. 2.3 mm) [46]. The combination thicker subcutaneous fascia and thinner skin implies that injury of female skin more easily breaches the fascial compartment.…”

“…Therefore, fascia-specific strategies may be a promising novel therapeutic landscape on which to prevent scars and enhance wound repair. One possible strategy will be to target fascial fibroblasts, which display molecular and functional features that are different from papillary and reticular dermal fibroblasts [29,46]. Fascial fibroblasts possess higher potency in proliferation and in collagen lattice contraction in vivo and hence are profibrotic and more active than dermal fibroblasts [79].…”

GDNF neurotrophic factor signalling determines the fate of dermal fibroblasts in wound‐induced hair neogenesis and skin regeneration

“…Spiny mice are notable for their ability to regenerate skin through wound‐induced hair neogenesis (WIHN). WIHN does occur in the house mouse, but only in severe wounds and to a much lesser extent 26–34 . During WIHN, a progeny of interfollicular, epidermal and dermal cells become ‘embryonic‐like’ to restore early epithelial‐mesenchymal interactions, resulting in the regeneration of hair follicles, fat and arrector pili muscle 35 .…”

The need to reassess single-cell RNA sequencing datasets: more is not always better

“…or reflect underlying functional/positional differences. [3][4][5][6] It is thus of utmost importance that the scientific community interested in a specific tissue or cell type agrees on the existing subsets within particular cell types and their defining molecular profiles, so that a common reference atlas may be used to understand homeostasis and response to varying insults. 7 In a re-analysis of 13,823 human adult dermal fibroblasts obtained from four independent scRNAseq studies, [8][9][10][11] we recently proposed that human skin presents a common set of fibroblast subsets, irrespective of donor area.…”