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.