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

Zhou,Zhi‑Qiang; Chen,Yi; Chai,Mi; Tao,Ran; Lei,Yong‑Hong; Jia,Yi‑Qing; Shu,Jun; Ren,Jing; Li,Guo; Wei,Wen‑Xin; Han,Yu‑Di; Han,Yan

doi:10.3892/ijmm.2018.4006

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

Authors:
- Zhi‑Qiang Zhou
- Yi Chen
- Mi Chai
- Ran Tao
- Yong‑Hong Lei
- Yi‑Qing Jia
- Jun Shu
- Jing Ren
- Guo Li
- Wen‑Xin Wei
- Yu‑Di Han
- Yan Han
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Affiliations: Department of Plastic and Reconstructive Surgery, General Hospital of Chinese PLA, Beijing 100853, P.R. China, Institute of Bioengineering, Academy of Military Medical Research, Academy of Military Science of Chinese PLA, Beijing 100071, P.R. China
Published online on: November 30, 2018 https://doi.org/10.3892/ijmm.2018.4006
Pages: 890-900
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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