Fang Jun-Ren, Chen Chun-Lin, Chen Yi-Qing, Luo Sheng-Kang
Second School of Clinical Medicine, Southern Medical University, Guangzhou City, Guangdong Province, China.
Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, 466 Middle Xin Gang Road, Guangzhou City, 510317, Guangdong Province, China.
Aesthetic Plast Surg. 2025 Feb;49(3):917-928. doi: 10.1007/s00266-024-04477-1. Epub 2024 Nov 4.
Keloid, scar caused by atypical wound repair, represents a significant difficulty for specialists in plastic surgery and dermatology. Adipose-derived mesenchymal stem cells (ADSCs) can regulate fibrotic phenotypes of keloid fibroblasts (KFs) in a paracrine fashion, but whether small extracellular vesicles (SEVs) are the key functional carrier in ADSC paracrine regulation of KFs remains unknown. This study aims to explore whether the regulatory effects of conditioned medium (CM) obtained from ADSCs on KFs can be impaired by decreased SEV content in the ADSC-CM.
Clinical specimens were utilized to extract keloid fibroblasts (KFs), normal fibroblasts (NFs), and adipose-derived stem cells (ADSCs). Fibroblasts were cultured with CM obtained from ADSCs untreated or treated with the sphingomyelinase inhibitor GW4869. The features of SEVs derived from ADSC-CM were characterized, and fibroblast proliferation, migration, apoptosis, and expression of ECM proteins were analyzed.
The sphingomyelinase inhibitor GW4869 successfully reduced the SEV content in ADSC-CM, and both control ADSC-CM and ADSC-CM with reduced SEV content significantly inhibited KF proliferation, migration, and α-SMA synthesis but not KF apoptosis, whereas only NF proliferation was inhibited by ADSC-CM. The reduced SEV content only affected the inhibition of KF proliferation induced by ADSC-CM.
ADSC-CM inhibits various fibrotic phenotypes of KFs, but decreasing the SEV content in ADSC-CM did not significantly alter the antifibrotic effects of ADSC-CM. Thus, SEVs may not be the key mediator of ADSCs paracrine regulation of KFs.
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瘢痕疙瘩是由非典型伤口修复引起的瘢痕，给整形外科和皮肤科专家带来了重大难题。脂肪间充质干细胞（ADSCs）可以通过旁分泌方式调节瘢痕疙瘩成纤维细胞（KFs）的纤维化表型，但小细胞外囊泡（SEVs）是否是ADSCs旁分泌调节KFs的关键功能载体仍不清楚。本研究旨在探讨ADSCs条件培养基（CM）中SEV含量降低是否会削弱其对KFs的调节作用。
利用临床标本提取瘢痕疙瘩成纤维细胞（KFs）、正常成纤维细胞（NFs）和脂肪干细胞（ADSCs）。将成纤维细胞与未处理或用鞘磷脂酶抑制剂GW4869处理的ADSCs获得的CM一起培养。对ADSC-CM来源的SEVs的特征进行了表征，并分析了成纤维细胞的增殖、迁移、凋亡以及细胞外基质蛋白的表达。
鞘磷脂酶抑制剂GW4869成功降低了ADSC-CM中的SEV含量，对照ADSC-CM和SEV含量降低的ADSC-CM均显著抑制KF增殖、迁移和α-SMA合成，但不影响KF凋亡，而ADSC-CM仅抑制NF增殖。SEV含量降低仅影响ADSC-CM对KF增殖的抑制作用。
ADSC-CM抑制KFs的多种纤维化表型，但降低ADSC-CM中的SEV含量并未显著改变ADSC-CM的抗纤维化作用。因此，SEVs可能不是ADSCs旁分泌调节KFs的关键介质。
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