Interleukin-10-Modified Adipose-Derived Mesenchymal Stem Cells Prevent Hypertrophic Scar Formation via Regulating the Biological Characteristics of Fibroblasts and Inflammation

Abstract

Hypertrophic scar causes serious functional and cosmetic problem, but no treatment method is known to achieve a satisfactory therapeutic effect. However, mesenchymal stem cells show a possible cure prospect. Here, we investigated the effect of interleukin-10-modified adipose-derived mesenchymal stem cells (IL-10-ADMSC) on the formation of hypertrophic scar. In vitro, IL-10-ADMSC could highly express IL-10 and exhibited stronger inhibition of hypertrophic scar fibroblasts (HSFs) proliferation, migration, and extracellular matrix synthesis (the expression of collagen I, collagen III, FN, and α-SMA protein) than ADMSC. In vivo, we found that IL-10-ADMSC speeded up wound healing time and reduced scar area and scar outstanding height. Same as in vitro, IL-10-ADMSC also exhibited stronger inhibition of extracellular matrix synthesis (the expression of collagen I, collagen III protein) in wound than ADMSC. In addition, we also found that IL-10-ADMSC is also a stronger inhibitory effect on inflammation in wound than ADMSC, and IL-10-ADMSC inhibited TGF-β/Smads and NF-κB pathway. In conclusion, IL-10-ADMSC demonstrated the ability to prevent hypertrophic scar formation. And its possible molecular mechanism might be related to IL-10-ADMSC inhibiting the proliferation and migration of the synthesis of extracellular matrix of HSFs, and IL-10-ADMSC inhibited the inflammation during the wound healing.

Dual CXCR4/IL-10 Gene-Edited Human Amniotic Mesenchymal Stem Cells Exhibit Robust Therapeutic Properties in Chronic Wound Healing

“…IL-10-gene-modified AMM cells show increased regenerative wound healing through multiple biological effects, such as enhancing angiogenesis, modulating inflammation, and regulating extracellular matrix remodeling [ 18 ]. In addition, IL-10-modified adipose MSCs prevent hypertrophic scar formation by regulating inflammation [ 19 ]. In line with these reports, our results showed that secretory factors derived from AMM/CI regulated phagocytosis and anti-inflammation in macrophages, indicating favorable effects on wound healing via the regulation of the inflammatory response.…”

TSG‐6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1α/TRAF2/NF‐κB signalling

“… 31 , 32 The administration of anti‐inflammatory treatments to wounded tissues at an early time point has the potential to protect against scar formation while driving more rapid healing responses, with cytokines serving as central regulators of HS‐related inflammation. 7 , 9 , 10 , 11 , 12 Here, TNF‐α, IL‐1β, and IL‐6 expression levels were found to be significantly elevated in HSFs under basal conditions, while TSG‐6 treatment suppressed the expression of all three of these cytokines, in line with prior evidence from a rabbit ear HS model system in which TSG‐6 was able to prevent scar formation in part via suppressing IL‐1β, IL‐6, and TNF‐α expression. 10 …”

“… 17 , 33 NF‐κB (p65) serves as a core transcriptional regulator of inflammation‐related gene expression, 34 , 35 with growing evidence suggesting that NF‐κB activation can promote pro‐inflammatory gene expression, thereby triggering inflammatory cascades that drive HS development. 9 , 11 , 12 Furthermore, NF‐κB acts as an important link between ER stress and inflammatory response. 15 , 33 While ER stress can thus induce IRE1α‐mediated inflammatory NF‐κB signalling, no prior studies have reported on the link between this signalling axis and HS formation.…”

“… 4 , 7 , 8 Anti‐inflammatory therapies thus represent a promising approach to preventing or treating HS development. 9 , 10 , 11 , 12 …”

“…These factors, in turn, drive fibroblasts to proliferate and secrete excessive levels of collagen, thus facilitating HS formation 4,7,8 . Anti‐inflammatory therapies thus represent a promising approach to preventing or treating HS development 9‐12 …”