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

Year 2022, , 324 - 334, 30.09.2022

Esra Arısu Naghavı Bakiye Goker Bagca , Senem Tekeli Gürkan Yiğittürk , Burak Gökçe , Canberk Tomruk , Türker Çavuşoğlu , Çığır Avcı , Cumhur Gündüz , Yiğit Uyanıkgil

https://doi.org/10.17343/sdutfd.1077520

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.

Keywords

Sirolimus, Ursodeoxycholic acid, Oxidative stress, Human adipose tissue-derived mesenchymal stem cells

Supporting Institution

Ege University Research Foundation

Project Number

2015/TIP/010

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

Abstract

Amaç
Organ nakli sonrası mezenkimal kök hücrelerin (MKH)
immünosupresif ilaçlarla birlikte kullanımı klinik uygulamalarda
dikkat çekici hale gelmektedir. Bununla
birlikte, ilaçlar MKH'leri olumsuz yönde etkilemektedir.
Antioksidan bir molekül olan ursodeoksikolik asit
(UDKA) bu etkileri tersine çevirebilecektir. Bu çalışmanın
amacı, sirolimus ve UDKA'nın bireysel ve kombinasyon
olarak uygulanmasının insan yağ dokusu
kaynaklı MKH'ler (YDKMKH) üzerindeki etkilerinin
incelenmesidir.
Gereç ve Yöntem
Etken maddelerin sitotoksik etkileri zamana ve doza
bağlı WST-1 testi ile değerlendirildi. Kombinasyon
etkileri, izobologram analizi kullanılarak belirlendi.
Apoptoz ve hücre döngüsünün değerlendirilmesi için
Muse hücre analizörü kullanıldı. Oksidatif stress belirteçlerinin
değişimi biyokimyasal yöntemle ölçüldü.
Bulgular
Sirolimusun IC50 dozu 48. saatte 18.58μM olarak
belirlendi. UDKA uygulanan doz aralığında sitotoksik
etki belirlenmediği için apoptoz, hücre döngüsü ve
oksidatif stres indikatör analizlerine 100 μM güvenli
doz ile devam edildi. Sirolimusun, apoptozu teşvik ettiği
ve hücre proliferasyonunu inhibe ettiği belirlendi.
UDKA'nın antioksidan özelliği ile sirolimusun YDKMKH'ler
üzerindeki apoptotik ve antiproliferatif etkilerini
azalttığı belirlendi.
Sonuç
Organ ve doku transplantasyonu sonrası immünosupresif
tedavi ile kombinasyon halinde UDKA tedavisinin
YDKMKH'ler üzerinde olumlu etkileri olabilecektir.

Keywords

sirolimus, ursodeoksikolik asit, oksidatif stres, insan yağ dokusu kaynaklı mezenkimal kök hücreler

Project Number

2015/TIP/010

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