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 embryonic-like stem cells, initially created from mouse adult fibroblasts. The current study demonstrated that iPSC-conditioned medium (iPSC-CM) may significantly suppress hypertrophic scar fibroblast activation. It was observed that in the presence of iPSC-CM, the level of collagen I was markedly reduced and α-smooth muscle actin, a marker for myofibroblasts (activated fibroblasts that mediate mechanical force-induced HS formation), exhibited a significantly lower level of expression in human dermal fibroblasts (HDFs) activated with transforming growth factor-β1. Additionally, iPSC-CM 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 iPSC-CM. These observations suggest that iPSC-CM 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.

Naringenin attenuates fibroblast activation and inflammatory response in a mechanical stretch-induced hypertrophic scar mouse model

“…The exaggerated inflammatory phase is closely associated with HS development, in which inflammatory cells such as neutrophils, macrophages and T-lymphocytes migrate to the wound site with high secretion of various cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and transforming growth factor (TGF)-β1 ( 7 , 9 , 10 ). Specific cytokines and inflammatory factors, such as TGF-β1, contribute to fibroblast activation and the modulation of the fibroblast phenotype ( 11 ). Many studies have reported that overactivation of dermal fibroblasts is involved in the process of HS formation ( 7 , 12 ).…”

Scar Management in the Pediatric and Adolescent Populations

“…The presence of induced pluripotent stem cellconditioned medium appears to reduce levels of type I (adult) collagen and attenuates the local inflammatory cell response in vitro. 103 Additionally, mesenchymal stromal cells may have the ability to be reprogrammed into sweat glandlike cells, offering the potential to restore injured adnexal structures from deep burn injuries. 104 …”

Suppressive effects of human fetal keratinocytes on the proliferation, differentiation and extracellular matrix synthesis of human hypertrophic scar fibroblasts in vitro

“…The role of miRNAs in skin development and pathology has been extensively researched. Several previous reports have indicated the involvement of miRNAs in the regulation of HS formation ( 11 , 28 – 30 ). However, limited information regarding the roles of miRNAs in fetal KC-induced alterations in HSFbs is available ( 31 ).…”