Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose‑derived stem cells into fibroblasts Retraction in /10.3892/ijmm.2024.5430

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

Retraction in: /10.3892/ijmm.2024.5430

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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1	Etich J, Bergmeier V, Pitzler L and Brachvogel B: Identification of a reference gene for the quantification of mRNA and miRNA expression during skin wound healing. Connect Tissue Res. 58:196–207. 2017. View Article : Google Scholar
2	Takeo M, Lee W and Ito M: Wound healing and skin regeneration. Cold Spring Harb Perspect Med. 5:a0232672015. View Article : Google Scholar : PubMed/NCBI
3	Canesso MC, Vieira AT, Castro TB, Schirmer BG, Cisalpino D, Martins FS, Rachid MA, Nicoli JR, Teixeira MM and Barcelos LS: Skin wound healing is accelerated and scarless in the absence of commensal microbiota. J Immunol. 193:5171–5180. 2014. View Article : Google Scholar : PubMed/NCBI
4	Tanno H, Kawakami K, Ritsu M, Kanno E, Suzuki A, Kamimatsuno R, Takagi N, Miyasaka T, Ishii K, Imai Y, et al: Contribution of invariant natural killer T cells to skin wound healing. Am J Pathol. 185:3248–3257. 2015. View Article : Google Scholar : PubMed/NCBI
5	Jackson WM, Nesti LJ and Tuan RS: Mesenchymal stem cell therapy for attenuation of scar formation during wound healing. Stem Cell Res Ther. 3:202012. View Article : Google Scholar : PubMed/NCBI
6	Schmidt BA and Horsley V: Intradermal adipocytes mediate fibroblast recruitment during skin wound healing. Development. 140:1517–1527. 2013. View Article : Google Scholar : PubMed/NCBI
7	Goldsmith EC, Bradshaw AD, Zile MR and Spinale FG: Myocardial fibroblast-matrix interactions and potential therapeutic targets. J Mol Cell Cardiol. 70:92–99. 2014. View Article : Google Scholar : PubMed/NCBI
8	Sriram G, Bigliardi PL and Bigliardi-Qi M: Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. Eur J Cell Biol. 94:483–512. 2015. View Article : Google Scholar : PubMed/NCBI
9	Warsinske HC, Ashley SL, Linderman JJ, Moore BB and Kirschner DE: Identifying mechanisms of homeostatic signaling in fibroblast differentiation. Bull Math Biol. 77:1556–1582. 2015. View Article : Google Scholar : PubMed/NCBI
10	Driskell RR, Lichtenberger BM, Hoste E, Kretzschmar K, Simons BD, Charalambous M, Ferron SR, Herault Y, Pavlovic G, Ferguson-Smith AC and Watt FM: Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature. 504:277–281. 2013. View Article : Google Scholar : PubMed/NCBI
11	Hassan WU, Greiser U and Wang W: Role of adipose-derived stem cells in wound healing. Wound Repair Regen. 22:313–325. 2014. View Article : Google Scholar : PubMed/NCBI
12	Shingyochi Y, Orbay H and Mizuno H: Adipose-derived stem cells for wound repair and regeneration. Expert Opin Biol Ther. 15:1285–1292. 2015. View Article : Google Scholar : PubMed/NCBI
13	Ritter A, Friemel A, Fornoff F, Adjan M, Solbach C, Yuan J and Louwen F: Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells. Oncotarget. 6:34475–34493. 2015. View Article : Google Scholar : PubMed/NCBI
14	Hu R, Ling W, Xu W and Han D: Fibroblast-like cells differentiated from adipose-derived mesenchymal stem cells for vocal fold wound healing. PLoS One. 9:e926762014. View Article : Google Scholar : PubMed/NCBI
15	Ayuk SM, Abrahamse H and Houreld NN: The role of photobiomodulation on gene expression of cell adhesion molecules in diabetic wounded fibroblasts in vitro. J Photochem Photobiol B. 161:368–374. 2016. View Article : Google Scholar : PubMed/NCBI
16	Goova MT, Li J, Kislinger T, Qu W, Lu Y, Bucciarelli LG, Nowygrod S, Wolf BM, Caliste X, Yan SF, et al: Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol. 159:513–525. 2001. View Article : Google Scholar : PubMed/NCBI
17	Galiano RD: Quantitative and reproducible murine model of excisional wound healing. Wound Repair Regen. 12:485–492. 2004. View Article : Google Scholar : PubMed/NCBI
18	Kusama K, Jiang Y, Toguchi M, Ohno J, Shikata H, Sakashita H and Sakagami H: Use of the monoclonal antibody M30 for detecting HSG cell apoptosis. Anticancer Res. 20:151–154. 2000.PubMed/NCBI
19	Liu H, Mu L, Tang J, Shen C, Gao C, Rong M, Zhang Z, Liu J, Wu X, Yu H and Lai R: A potential wound healing-promoting peptide from frog skin. Int J Biochem Cell Biol. 49:32–41. 2014. View Article : Google Scholar : PubMed/NCBI
20	Caruana G, Bertozzi N, Boschi E, Pio Grieco M, Grignaffini E and Raposio E: Role of adipose-derived stem cells in chronic cutaneous wound healing. Ann Ital Chir. 86:1–4. 2015.PubMed/NCBI
21	Kim WS, Park BS, Sung JH, Yang JM, Park SB, Kwak SJ and Park JS: Wound healing effect of adipose-derived stem cells: A critical role of secretory factors on human dermal fibroblasts. J Dermatol Sci. 48:15–24. 2007. View Article : Google Scholar : PubMed/NCBI
22	Daniunaite K, Serenaite I, Misgirdaite R, Gordevicius J, Unguryte A, Fleury-Cappellesso S, Bernotiene E and Jarmalaite S: Epigenetic regulation of human adipose-derived stem cells differentiation. Mol Cell Biochem. 410:111–120. 2015. View Article : Google Scholar : PubMed/NCBI
23	Mahmoudifar N and Doran PM: Mesenchymal stem cells derived from human adipose tissue. Methods Mol Biol. 1340:53–64. 2015. View Article : Google Scholar : PubMed/NCBI
24	Huang SJ, Fu RH, Shyu WC, Liu SP, Jong GP, Chiu YW, Wu HS, Tsou YA, Cheng CW and Lin SZ: Adipose-derived stem cells: Isolation, characterization, and differentiation potential. Cell Transplant. 22:701–709. 2013. View Article : Google Scholar
25	Gao S, Zhao P, Lin C, Sun Y, Wang Y, Zhou Z, Yang D, Wang X, Xu H, Zhou F, et al: Differentiation of human adipose-derived stem cells into neuron-like cells which are compatible with photocurable three-dimensional scaffolds. Tissue Eng Part A. 20:1271–1284. 2014. View Article : Google Scholar :
26	Rodriguez J, Boucher F, Lequeux C, Josset-Lamaugarny A, Rouyer O, Ardisson O, Rutschi H, Sigaudo-Roussel D, Damour O and Mojallal A: Intradermal injection of human adipose-derived stem cells accelerates skin wound healing in nude mice. Stem Cell Res Ther. 6:2412015. View Article : Google Scholar : PubMed/NCBI
27	Guneta V, Loh QL and Choong C: Cell-secreted extracellular matrix formation and differentiation of adipose-derived stem cells in 3D alginate scaffolds with tunable properties. J Biomed Mater Res A. 104:1090–1101. 2016. View Article : Google Scholar : PubMed/NCBI
28	Reilly GC and Engler AJ: Intrinsic extracellular matrix properties regulate stem cell differentiation. J Biomech. 43:55–62. 2010. View Article : Google Scholar
29	Dzobo K, Turnley T, Wishart A, Rowe A, Kallmeyer K, van Vollenstee FA, Thomford NE, Dandara C, Chopera D, Pepper MS and Parker MI: Fibroblast-derived extracellular matrix induces chondrogenic differentiation in human adipose-derived mesenchymal stromal/stem cells in vitro. Int J Mol Sci. 17:E12592016. View Article : Google Scholar : PubMed/NCBI
30	Park IS, Chung PS and Ahn JC: Adipose-derived stromal cell cluster with light therapy enhance angiogenesis and skin wound healing in mice. Biochem Biophys Res Commun. 462:171–177. 2015. View Article : Google Scholar : PubMed/NCBI
31	Shokrgozar MA, Fattahi M, Bonakdar S, Ragerdi Kashani I, Majidi M, Haghighipour N, Bayati V, Sanati H and Saeedi SN: Healing potential of mesenchymal stem cells cultured on a collagen-based scaffold for skin regeneration. Iran Biomed J. 16:68–76. 2012.PubMed/NCBI
32	Desai VD, Hsia HC and Schwarzbauer JE: Reversible modulation of myofibroblast differentiation in adipose-derived mesenchymal stem cells. PLoS One. 9:e868652014. View Article : Google Scholar : PubMed/NCBI
33	Grabska-Liberek I, Galus R, Owczarek W, Wlodarsk K, Zabielski S, Malejczyk J and Sladowski D: Collagen based dressings in the treatment of wound healing. Pol Merkur Lekarski. 35:51–54. 2013.In Polish. PubMed/NCBI
34	Jabłońska-Trypuć A, Matejczyk M and Rosochacki S: Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem. 31:177–183. 2016. View Article : Google Scholar
35	Sivan U, Jayakumar K and Krishnan LK: Matrix-directed differentiation of human adipose-derived mesenchymal stem cells to dermal-like fibroblasts that produce extracellular matrix. J Tissue Eng Regen Med. 10:E546–E558. 2016. View Article : Google Scholar
36	Rolin GL, Binda D, Tissot M, Viennet C, Saas P, Muret P and Humbert P: In vitro study of the impact of mechanical tension on the dermal fibroblast phenotype in the context of skin wound healing. J Biomech. 47:3555–3561. 2014. View Article : Google Scholar : PubMed/NCBI
37	Pericacho M, Velasco S, Prieto M, Llano E, López-Novoa JM and Rodriguez-Barbero A: Endoglin haploinsufficiency promotes fibroblast accumulation during wound healing through Akt activation. PLoS One. 8:e546872013. View Article : Google Scholar : PubMed/NCBI