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

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. [ABSTRACT FROM AUTHOR]