URSODEOKSİKOLİK ASİTİN SİROLİMUS UYGULANAN YAĞ DOKUSU KÖKENLİ MEZENKİMAL KÖK HÜCRELER ÜZERİNE ETKİLERİNİN İNCELENMESİ

Abstract

Objective: The usage of mesenchymal stem cells (MSC) with immunosuppressive drugs after organ transplantation is becoming remarkable in clinical applications. However, the drugs negatively affect MSCs. Ursodeoxycholic acid (UDCA), which is an antioxidant molecule, may reverse these effects.The aim of this study is to investigate the molecular effects of sirolimus and UDCA on human adipose tissue-derived MSCs (ADMSCs) individually and in combination. Material and Methods: The cytotoxic effects of the active substances were evaluated by time and dose-dependent WST-1 test. The combinational effects were determined using isobologram analysis. Muse cell analyzer was used for the evaluation of apoptosis and cell cycle. Lipid peroxidation, superoxide dismutase activity, catalase activity, glutathione peroxidase activity were measured by biochemical methods. Results: IC50 dose of sirolimus was determined as 18.58μM in the 48th hour. Because no cytotoxic effect was observed at the studied doses of UDCA, the apoptosis, cell cycle, and oxidative stress indicator analyses were continued with a safe dose of 100 μM. Sirolimus promoted apoptosis and inhibited cell proliferation. It was determined that UDCA reduced the apoptotic and anti-proliferative effects of sirolimus on ADMSCs with its anti-oxidant property. Conclusion: The UDCA treatment in combination with immunosuppressive therapy after organ and tissue transplantation may have positive effects on ADMSCs.