INVESTIGATION OF URSODEOXYCHOLIC ACID EFFECTS ON SIROLIMUS TREATED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS

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 study aims
 that to determine the effects of sirolimus and UDCA
 on human adipose tissue-derived MSCs (ADMSCs)
 individually and in combination.
 Material and Method
 The cytotoxicity of the agents was evaluated by
 WST-1 test in time and dose-dependent manner.
 The combinational effects were determined using
 isobologram analysis. Muse cell analyzer was used for
 the evaluation of apoptosis and cell cycle. Oxidative
 stress markers 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.