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冻干脂肪来源干细胞浓缩条件培养基与多糖水凝胶联合抑制增生性瘢痕形成

Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring.

作者信息

Zhang Chaoyu, Wang Ting, Zhang Li, Chen Penghong, Tang Shijie, Chen Aizhen, Li Ming, Peng Guohao, Gao Hangqi, Weng Haiyan, Zhang Haoruo, Li Shirong, Chen Jinghua, Chen Liangwan, Chen Xiaosong

机构信息

Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, China.

出版信息

Stem Cell Res Ther. 2021 Jan 7;12(1):23. doi: 10.1186/s13287-020-02061-3.

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.

摘要

背景

基于间充质干细胞的无细胞疗法已被广泛应用于治疗增生性瘢痕。然而,局部用药期间维持剂量低和治疗效果短暂仍是一个棘手的问题。在此,本研究旨在优化脂肪来源干细胞条件培养基(ADSC-CM)在预防增生性瘢痕形成方面的疗效。

方法

在本研究中,通过冷冻干燥程序浓缩ADSC-CM。在体外对不同剂量组(CM、CM5、CM10)对人瘢痕疙瘩成纤维细胞(HKF)的增殖、凋亡和α平滑肌肌动蛋白(α-SMA)表达的疗效进行了研究。在兔耳体内研究了将脂肪来源干细胞浓缩条件培养基(ADSCC-CM)掺入多糖水凝胶中的情况。进行苏木精-伊红(H&E)和Masson三色染色以评估瘢痕增生。

结果

我们注意到ADSCC-CM可以剂量依赖性方式下调HKF的α-SMA表达。在兔耳模型中,在观察的4个月内,中剂量组(CM5)和高剂量组(CM10)的瘢痕增生受到抑制,瘢痕隆起指数(SEI)降低。值得注意的是,CM5与多糖水凝胶(CM5+H)联合对瘢痕增生产生了最佳预防效果。简而言之,CM5+H组的黑色素、高度、血管化和柔韧性均优于对照组。胶原蛋白分布均匀,皮肤附属器可以再生。

结论

总之,ADSCC-CM由于其抗纤维化作用可下调α-SMA的表达,并促进胶原纤维的重排,这对于瘢痕预防至关重要。ADSCC-CM与多糖水凝胶的原位交联可以显著提高抑制瘢痕增殖的治疗效果。因此,ADSCC-CM与水凝胶的联合可能成为增生性瘢痕预防的潜在替代方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fa/7792059/8834b4a4c269/13287_2020_2061_Fig1_HTML.jpg

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