Collagen cross‐linking by adipose‐derived mesenchymal stromal cells and scar‐derived mesenchymal cells: Are mesenchymal stromal cells involved in scar formation?

Abstract

In this work, different fibroblast-like (mesenchymal) cell populations that might be involved in wound healing were characterized and their involvement in scar formation was studied by determining collagen synthesis and processing. Depending on the physical and mechanical properties of the tissues, specific collagen cross-linking routes are followed. In skin the cross-linking of the pyridinium type is normally very low; however, in different forms of fibrosis increased levels of this type of cross-linking have been found. The enzyme lysyl hydroxylase-2b (LH-2b) plays a crucial role in this type of cross-linking. The gene expression levels of LH-2b, alpha-smooth muscle actin, and collagen types I and III were determined in dermis, subcutaneous fat, and (hypertrophic) scar tissue as well as in isolated cultured mesenchymal cells derived from these tissues, by real-time RT-polymerase chain reaction. Cultured mesenchymal cells from fat and scar tissue as well as the tissues itself showed significantly higher expression of LH-2b, alpha-SMA, and collagen type I than dermal mesenchymal cells. LH-2b-dependent pyridinium cross-linking was significantly enhanced in fat and scar tissue compared with dermis. FACS analysis was performed to characterize the fibroblast-like cells from the dermis, fat, and scar tissue. All cell populations express the distinct pattern of CD markers also expressed by mesenchymal stromal cells. Furthermore, parts of these cell populations were able to differentiate into adipocytes, chondrocytes, and osteoblasts. We conclude, therefore, that mesenchymal (stem) cells from the subcutaneous fat might be responsible for the accumulation of collagen in these scars.

Influence of different commercial scaffolds on the in vitro differentiation of human mesenchymal stem cells to nucleus pulposus-like cells

“…In the case of implantation of a substantial number of stem cells, such conditions can lead to cell death rather than cell differentiation and matrix production. Additionally, after the removal of degenerated disc tissue, the implanted cells may need too much time to differentiate and generate new disc tissue and a more probable scenario might be that undesired scar tissue is formed instead [17].…”

Development, validation and testing of a human tissue engineered hypertrophic scar model

“…The second aim of this study was to validate the HTscar model with two therapeutics regularly used in the clinic for scar treatment (5FU and tC) (Wang et al, 2009) and one therapeutic known to be unsuccessful in scar reduction (VitD3) (van der Veer et al, 2009b). Supplementing the Htscar model with 5FU resulted in partial normalization of the contraction and the epidermal thickness.…”

“…In vitro cell culture models have been used to gain insight into different aspects of scar pathogenesis. Adipose derived mesenchymal cells, for example, have been described as having a number of similar characteristics to mesenchymal cells found within HTscar tissue, e.g., both are α-SMA positive (El-Ghalbzouri et al, 2004;van den Bogaerdt et al, 2009;van der Veen et al, 2011;Wang et al, 2008). Additionally, a scratch assay has been described in which an increase in the single parameter Connective tissue Growth Factor (CtGF) has been proposed for testing scar therapeutics (Moon et al, 2012).…”

“…In order to develop, validate, and further test the HTscar model, a number of quantifiable parameters typical for HTscars were identified: 1) contraction, since HTscars are highly contractile (Ehrlich et al, 1994); 2) thickness of the dermis; 3) collagen-1 secretion, since more connective tissue is formed in Htscars than in Ntscars (van der Veer et al, 2009a); 4) the degree of epithelialization, since it has been described that the extent of HTscar formation corresponds with delayed wound closure (Deitch et al, 1983); and 5) thickness of the regenerating epidermis, since it is known that HTscars have more epidermal cell layers than Ntscars (Andriessen et al, 1998). In addition to the scar forming parameters, we assessed the secretion of two cytokines known to contribute to wound healing, IL-6 and CXCL8 (Broughton et al, 2006).…”

“…In addition to the scar forming parameters, we assessed the secretion of two cytokines known to contribute to wound healing, IL-6 and CXCL8 (Broughton et al, 2006). The HTscar model was validated with therapeutics generally used in the clinic for scar treatment (5-fluorouracil and a triamcinolone (Kenacort ® -A40)) (Mustoe et al, 2002;Wang et al, 2009) and a therapeutic known to be unsuccessful in scar reduction (1,25-dihydroxy vitamin D3) (van der Veer et al, 2009b). the HTscar model was further tested with two potential scar-reduction therapeutics (all-trans-retinoic acid and atorvastatin calcium salt trihydrate) (Aarons et al, 2007;Wang et al, 2009).…”