The cytotoxicity of advanced glycation end products was attenuated by UCMSCs in human vaginal wall fibroblasts by inhibition of an inflammatory response and activation of PI3K/AKT/PTEN

Abstract

Pelvic organ prolapse (POP) occurs when the pelvic organs (bladder, bowel or uterus) herniate into the vagina, causing incontinence, voiding, and bowel and sexual dysfunction, negatively impacting upon a woman's quality of life. Intermediate intermolecular cross-links and advanced glycation cross-links increase in prolapsed tissue. Stem cells are able to participate in tissue repair due to their ability to differentiate into multiple lineages, and thus into various types of connective tissue cells, so they therefore hold great promise for treating pelvic floor dysfunction. The current study found that advanced glycation end products (AGEs) inhibited the viability and proliferation of human vaginal wall fibroblasts (VWFs), were cytotoxic to VWFs, and also induced the apoptosis of VWFs. In contrast, umbilical cord-derived mesenchymal stem cells (UCMSCs) secreted anti-inflammation cytokines to protect against the cytotoxic effects of fibroblasts induced by AGEs and attenuated the cytotoxic effect of AGE on fibroblasts by activation of the PI3K/Akt-PTEN pathway. This study demonstrated that UCMSCs inhibited the cytotoxic effect of AGE in cells from patients with POP by inducing an anti-inflammatory reaction and activating the PI3K/AKT/PTEN signaling pathway. The current results provide important insights into use of stem cells to treat POP.