Adipose-derived Stem Cells Antagonize Fibrotic Response of Keloid-derived Fibroblasts

Keloid is an excessive fibrotic condition that results in excessive deposition of extracellular matrix (ECM), mainly composed of collagen. Transforming growth factor-β (TGF-β) is a cytokine involved in keloid development by stimulating ECM production and fibrosis. Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells that regulate the immune response. Adipose-derived stem cells (ADSCs), which are MSCs, are present in the stromal portion of the adipose tissue and are accessible for clinical use.

This study aimed to investigate the effects of ADSCs on the fibrotic responses of keloid-derived fibroblasts.

Keloid-derived fibroblasts cultured in the presence of transforming growth factor-β-1 (TGF-β1) were co-cultured with ADSCs. Immunofluorescence microscopy, real-time polymerase chain reaction, and western blotting were performed to determine the expression levels of smooth muscle protein 22-α (SM22α), type I collagen (COL1), TGF-β1, matrix metallopeptidase 2 (MMP2), SMAD2, SMAD3, platelet-derived growth factor receptor α (PDGFRα), and TGF-β receptor type-1 (TGFβR1). Keloid-derived fibroblast-embedded collagen gel contraction assay was also performed.

Keloid-derived fibroblasts express SM22α, COL1, TGF-β1, MMP2, SMAD2, SMAD3, PDGFRα, and TGFβR1. TGF-β1 increased their expression levels, whereas ADSCs significantly suppressed them. TGF-β1 induced the contraction of keloid-derived fibroblast-embedded collagen gel, whereas ADSCs significantly inhibited it.

ADSCs antagonize the fibrotic effects of TGF-β on keloid-derived fibroblasts and may be a therapeutic agent for keloids. ADSCs may also suppress keloid development during normal wound healing.