Chaoyu Zhang1,2,3, Ting Wang1,2, Li Zhang4, Penghong Chen1,2,3, Shijie Tang1,2,3, Aizhen Chen1,2,3, Ming Li1,2, Guohao Peng1,2,3, Hangqi Gao1,2, Haiyan Weng1,2, Haoruo Zhang1,2, Shirong Li5, Jinghua Chen6, Liangwan Chen7, Xiaosong Chen8,9. 1. Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. 2. Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, China. 3. Department of Stem Cell Research Institute, Fujian Medical University, Fuzhou, China. 4. Department of Central Sterile Supply, Fujian Medical University Union Hospital, Fuzhou, China. 5. Department of Plastic and Reconstructive Surgery, Southwestern Hospital, Army Military Medical University, Chongqing, China. 6. Department of Pharmaceutical Analysis, The School of Pharmacy, Fujian Medical University, Fuzhou, China. 7. Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China. chenliangwan@fjmu.edu.cn. 8. Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, China. chenxiaosong74@163.com. 9. Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, China. chenxiaosong74@163.com.
Abstract
BACKGROUND: Mesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scars. However, low maintenance dose and transitory therapeutic effects during topical medication remain a thorny issue. Herein, this study aimed to optimize the curative effect of adipose-derived stem cell conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring. METHODS: In the present study, ADSC-CM was concentrated via the freeze-drying procedure. The efficacy of different dose groups (CM, CM5, CM10) was conducted on the proliferation, apoptosis, and α-smooth muscle actin (α-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cell concentrated conditioned medium (ADSCC-CM) into polysaccharide hydrogel was investigated in rabbit ear, in vivo. Haematoxylin-eosin (H&E) and Masson's trichrome staining were performed for the evaluation of scar hyperplasia. RESULTS: We noted that ADSCC-CM could downregulate the α-SMA expression of HKFs in a dose-dependent manner. In the rabbit ear model, the scar hyperplasia in the medium-dose group (CM5) and high-dose group (CM10) was inhibited with reduced scar elevation index (SEI) under 4 months of observation. It is noteworthy that the union of CM5 and polysaccharide hydrogel (CM5+H) yielded the best preventive effect on scar hyperplasia. Briefly, melanin, height, vascularity, and pliability in the CM5+H group were better than those of the control group. Collagen was evenly distributed, and skin appendages could be regenerated. CONCLUSIONS: Altogether, ADSCC-CM can downregulate the expression of α-SMA due to its anti-fibrosis effect and promote the rearrangement of collagen fibres, which is integral to scar precaution. The in situ cross bonding of ADSCC-CM and polysaccharide hydrogel could remarkably enhance the therapeutic outcomes in inhibiting scar proliferation. Hence, the alliance of ADSCC-CM and hydrogel may become a potential alternative in hypertrophic scar prophylaxis.
BACKGROUND: Mesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scars. However, low maintenance dose and transitory therapeutic effects during topical medication remain a thorny issue. Herein, this study aimed to optimize the curative effect of adipose-derived stem cell conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring. METHODS: In the present study, ADSC-CM was concentrated via the freeze-drying procedure. The efficacy of different dose groups (CM, CM5, CM10) was conducted on the proliferation, apoptosis, and α-smooth muscle actin (α-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cell concentrated conditioned medium (ADSCC-CM) into polysaccharide hydrogel was investigated in rabbit ear, in vivo. Haematoxylin-eosin (H&E) and Masson's trichrome staining were performed for the evaluation of scar hyperplasia. RESULTS: We noted that ADSCC-CM could downregulate the α-SMA expression of HKFs in a dose-dependent manner. In the rabbit ear model, the scar hyperplasia in the medium-dose group (CM5) and high-dose group (CM10) was inhibited with reduced scar elevation index (SEI) under 4 months of observation. It is noteworthy that the union of CM5 and polysaccharide hydrogel (CM5+H) yielded the best preventive effect on scar hyperplasia. Briefly, melanin, height, vascularity, and pliability in the CM5+H group were better than those of the control group. Collagen was evenly distributed, and skin appendages could be regenerated. CONCLUSIONS: Altogether, ADSCC-CM can downregulate the expression of α-SMA due to its anti-fibrosis effect and promote the rearrangement of collagen fibres, which is integral to scar precaution. The in situ cross bonding of ADSCC-CM and polysaccharide hydrogel could remarkably enhance the therapeutic outcomes in inhibiting scar proliferation. Hence, the alliance of ADSCC-CM and hydrogel may become a potential alternative in hypertrophic scar prophylaxis.
Authors: Michael W Hughes; Ting-Xin Jiang; Maksim V Plikus; Christian Fernando Guerrero-Juarez; Chien-Hong Lin; Christopher Schafer; Robert Maxson; Randall B Widelitz; Cheng-Ming Chuong Journal: J Invest Dermatol Date: 2018-03-23 Impact factor: 8.551