Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks

Abstract

Objective Stretch marks are disfiguring skin lesions that often cause problems of self‐esteem, but little effort has been put to studying this pathology. We therefore analysed cell cultures of dermal fibroblasts isolated from a striae albae, to thereafter reconstruct a full thickness skin model. Methods Human Dermal Fibroblasts (HDF) were isolated from a striae distensae (SD) lesion and from the adjacent non‐lesioned skin. The dermis of two full thickness skin models was reconstructed with either striae‐ or normal‐HDF, while the epidermis was in both reconstructed with Normal Human Epidermal Keratinocytes. Results Main observations and pertinent data: Gene expression analysis of cell cultures revealed a generalized decomposition of the Extra Cellular Matrix (ECM), since collagens type I and III, lysyl oxidase (LOX), biglycan, lumican and fibronectin were downregulated, while MMP3 was increased together with a decrease of its natural inhibitors (TIMP1, TIMP2 and PAI‐1). These findings were statistically corroborated for key ECM elements at the protein level (COL1, MMP1 and TGFB1). Interestingly, striae albae fibroblasts retained a pro‐inflammatory phenotype, as suggested by increased gene expression of CXCL8, HAS1 and TNFA. We next reconstructed a full thickness skin model (Striae Reconstructed) with dermal fibroblasts from striae albae. Gene expression analysis showed that the Striae Reconstructed elicited not only ECM decomposition, but also skin ageing, as indicated by the upregulation of P16, PTGS2 and SOD2. Discussion points: Although the epidermis was constructed with normal human epidermal keratinocytes, the Striae Reconstructed presented epidermal atrophy and a dramatic increase of β1‐integrin at the epidermal‐dermal junction providing, for the first time to our knowledge, a rationale showing that the key cell player behind stretch marks are dermal fibroblasts rather than epidermal keratinocytes. Conclusion New knowledge: Taken together, our findings shed new light into the aetiology of stretch marks and indicate that the Striae Reconstructed, a new model for in vitro testing and drug screening, may open new avenues for the treatment of stretch marks.

The Alleviating Effect of Lagerstroemia indica Flower Extract on Stretch Marks through Regulation of Mast Cells

“…We first examined the effect on normal human dermal fibroblasts (NHDFs) of treating conditioned medium (CM) from RBL-2H3 in response to antigen-bound IgE. A previous report found that the genes related to the decomposition of ECM and pro-inflammation were changed in the HDF isolated from a SD lesion [8]. Figure 5 shows that consistent with this, we found that most ECM components were decreased in the NHDF treated with the CM from RBL-2H3 in response to antigen-bound IgE, when compared to non-treated NHDF.…”

“…Table 1 lists the primer sequences. The primer sequences of all genes used in Figures 5 and 6 followed the method of Perez-Aso et al [8].…”

“…Thinned epidermis is shown with a flattening of the rete pegs [1,5,6]. The reorganization of collagen, FN, ELN, and FBN are thought to be a key cause in SD pathogenesis, and these genes are used as genetic markers for SD [7,8].…”

Tasmannia lanceolata leaf extract alleviates stretch mark appearance in a randomized, placebo‐controlled clinical trial in women and stimulates extracellular matrix synthesis in ex vivo human skin explants

“…10 A study comparing human dermal fibroblasts isolated from an SD lesion to those from the adjacent normal skin revealed a generalized altered composition of the extracellular matrix and notably a huge decrease in collagen type I and TGF-β1 protein levels, in parallel to overexpression of certain inflammatory markers such as TNF-α. 10 Because of their high prevalence and their psychosocial impact, there is a growing demand for an effective treatment for SD. So far, a large and diversified panel of topical treatments is offered to prevent or correct SD.…”

“…Indeed, numerous studies confirm that fibroblasts play a key role in the pathogenesis of stretch marks because they progressively become functionally dormant and present altered contractile forces in SD areas 8,9 . Furthermore, the transforming growth factor‐β (TGF‐ß), an activator of fibroblasts and type 1 collagen synthesis, is reported to be downregulated in stretch marks 10 . A study comparing human dermal fibroblasts isolated from an SD lesion to those from the adjacent normal skin revealed a generalized altered composition of the extracellular matrix and notably a huge decrease in collagen type I and TGF‐β1 protein levels, in parallel to overexpression of certain inflammatory markers such as TNF‐α 10 .…”