Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose‑derived stem cells into fibroblasts

Abstract

Fibroblasts are the major effector cells of skin wound healing. Adipose-derived stem cells can differentiate into fibroblasts under certain conditions. In the present study, it was hypothesized that adipose-derived stem cells (ADSCs) could be induced by the adipose extracellular matrix (ECM) to differentiate into fibroblasts in order to promote skin wound healing. First, flow cytometry was used to detect the ratio of fibroblasts and relative expression of the fibroblast markers cytokeratin 19 (CK19) and vimentin in ADSCs. Then, the effect of the adipose ECM during the differentiation of ADSCs into fibroblasts was investigated by detecting the total amount of collagen fibers and degree of fibrosis, and the proliferation and cell cycle of differentiated fibroblasts, using the MTT assay and flow cytometry analysis respectively. Finally, a mouse skin wound model was established and treated with PBS, ADSC suspension or ECM + ADSCs to compare wound healing rate and expression of collagen I and collagen III by immunohistochemistry. Following induction of ADSCs with the adipose ECM, more fibroblasts were found, expression of CK19 and vimentin increased, and a greater degree of fibrosis occurred, which revealed the positive effect of the adipose ECM on the differentiation of ADSCs into fibroblasts. In addition, the induced fibroblasts had enhanced proliferation activity, with more cells in the S phase and fewer in the G2/M phase. The in vivo experiment indicated that the ECM produced by the ADSCs had a faster wound healing rate and increased expression of collagen I and collagen III compared with mice injected with PBS or ADSCs alone, which verified that ADSCs induced by the adipose ECM had a positive effect on skin wound healing. The present study demonstrated that the adipose ECM in combination with ADSCs may be a novel therapeutic target for the repair of skin injury, due to the ability of the adipose ECM to induce the differentiation of ADSCs into fibroblasts and to facilitate the wound healing process.

Exosomal vimentin from adipocyte progenitors accelerates wound healing

“…The cytoskeletal protein vimentin has been shown to act as a critical regulator of the wound healing process in different tissues and cell types (Cheng et al, 2016;Walker et al, 2018). Induction of ADCs with adipose ECM increased the expression of vimentin and the proportion of fibroblasts (Zhou et al, 2019). Consistent with these reports, the expression levels of vimentin significantly increased in various skin cell types treated with the stem cell secretome (Park et al, 2018).…”

Anti-Ageing Protein β-Klotho Rejuvenates Diabetic Stem Cells for Improved Gene-Activated Scaffold Based Wound Healing

“…Collagen IV represents a major component of the basement membrane and is essential for stable maturation of cells [ 60 ], while collagen VI anchors other matrix proteins such as fibronectin and collagen IV to regulate cell motility [ 61 ]. These ECM components can directly influence cell growth, differentiation and tissue regeneration [ 62 ]. Moreover, an increase in collagen deposition is a feature of enhanced healing in vivo [ 63 ].…”

Renal Progenitor Cells Have Higher Genetic Stability and Lower Oxidative Stress than Mesenchymal Stem Cells during In Vitro Expansion

“…The cells were thawed, and the initial viability was immediately evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The cells were seeded in 24 wells, each well randomly trypsinized and submitted to the new MTT assay in DMEM High Glucose® (Invitrogen™, USA) in the ratio of 1 : 9 every 72 hours, as described by Zhou et al [ 24 ].…”