Suppressive effects of induced pluripotent stem cell-conditioned medium on in vitro hypertrophic scarring fibroblast activation.

ABSTRACT

Hypertrophic scarring (HS) is a type of fibrosis that occurs in the skin, and is characterized by fibroblast activation and excessive collagen production. However, at present, therapeutic strategies for this condition are ineffective. Previous studies have identified that the mutual regulation of chronic inflammation, mechanical force and fibroblast activation leads to the formation of HS. Induced pluripotent stem cells (iPSCs) are novel bioengineered embryonic­like stem cells, initially created from mouse adult fibroblasts. The current study demonstrated that iPSC­conditioned medium (iPSC­CM) may significantly suppress hypertrophic scar fibroblast activation. It was observed that in the presence of iPSC­CM, the level of collagen I was markedly reduced and α­smooth muscle actin, a marker for myofibroblasts (activated fibroblasts that mediate mechanical force­induced HS formation), exhibited a significantly lower level of expression in human dermal fibroblasts (HDFs) activated with transforming growth factor­ß1. Additionally, iPSC­CM attenuated the local inflammatory cell response by blocking the adhesion of human acute monocytic leukemia cell monocytes and fibroblasts in vitro. In addition, the contractile ability of HDFs may be reduced by iPSC­CM. These observations suggest that iPSC­CM may protect against processes leading to hypertrophic scarring by attenuating fibroblast activation, blocking inflammatory cell recruitment and adhesion and reducing the contractile ability of fibroblasts.