Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway

Abstract

Background: Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating skin wounds. However, the exact effects of hAMSCs on the healing of thermal burn skin wounds and their potential mechanisms are not explored. Methods: hAMSCs were isolated from amniotic membrane and characterized by RT-PCR, flow cytometry, immunofluorescence, and tumorigenicity test. We assessed the effects of hAMSCs and hAMSC conditional medium (CM) on wound healing in a deep second-degree burn injury model of mice. We then investigated the biological effects of hAMSCs and hAMSC-CM on the apoptosis and proliferation of heat stress-injured human keratinocytes HaCAT and dermal fibroblasts (DFL) both in vivo and in vitro. Next, we explored the underlying mechanisms by assessing PI3K/AKT and GSK3β/β-catenin signaling pathways in heat injured HaCAT and DFL cells after hAMSCs and hAMSC-CM treatments using PI3K inhibitor LY294002 and β-catenin inhibitor ICG001. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may activate PI3K/AKT signaling pathway.

PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities

“…Gsk3β is a typical regulation of the negative Wnt signaling pathway. Many researchers have described PI3K/AKT and Gsk3β/β-catenin signals as playing a key role in skin development and wound healing [44]. Based on the findings of previous studies, Gsk3β/β-catenin and PI3K/Akt signaling pathway was selected for verification.…”

hPMSCs protects against D-galactose-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling

“…Similarly, a D-gal-induced decline in Akt phosphorylation was also found in human umbilical vein endothelial cells [46]. Recently, Li et al reported that human amniotic MSCs e ciently ameliorate heat stress-induced skin injury by inhibiting apoptosis in skin cells through activating the Akt signaling pathway [47]. Based on these studies, we hypothesized that Akt/GSK-3β/Fyn pathway is involved in hPMSCs induced Nrf2 activation in senescent CD4 + T cells.…”

hPMSCs protects against aging-induced oxidative damage of CD4+ T cells through activating Akt-mediated Nrf2 antioxidant signaling

“…Similarly, a D-gal-induced decline in Akt phosphorylation was also found in human umbilical vein endothelial cells [45]. Recently, Li et al reported that human amniotic MSCs e ciently ameliorate heat stress-induced skin injury by inhibiting apoptosis in skin cells through activating the Akt signaling pathway [46]. Based on these studies, we hypothesized that Akt/GSK-3β/Fyn pathway is involved in hPMSCs induced Nrf2 activation in senescent CD4 + T cells.…”