sdü tıp fak derg Medical Journal of Süleyman Demirel University 2602-2109 Süleyman Demirel Üniversitesi 10.17343/sdutfd.1077520 Clinical Sciences Klinik Tıp Bilimleri URSODEOKSİKOLİK ASİTİN SİROLİMUS UYGULANAN YAĞ DOKUSU KÖKENLİ MEZENKİMAL KÖK HÜCRELER ÜZERİNE ETKİLERİNİN İNCELENMESİ INVESTIGATION OF URSODEOXYCHOLIC ACID EFFECTS ON SIROLIMUS TREATED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS https://orcid.org/0000-0003-1663-6970 Arısu Naghavı Esra EGE UNIVERSITY https://orcid.org/0000-0002-5714-7455 Goker Bagca Bakiye AYDIN ADNAN MENDERES UNIVERSITY https://orcid.org/0000-0002-9586-341X Tekeli Senem EGE UNIVERSITY https://orcid.org/0000-0002-5315-253X Yiğittürk Gürkan MUGLA SITKI KOCMAN UNIVERSITY https://orcid.org/0000-0002-7038-6434 Gökçe Burak EGE UNIVERSITY https://orcid.org/0000-0002-3810-3705 Tomruk Canberk EGE UNIVERSITY https://orcid.org/0000-0001-7100-7080 Çavuşoğlu Türker EGE UNIVERSITY https://orcid.org/0000-0001-8251-4520 Avcı Çığır EGE UNIVERSITY https://orcid.org/0000-0002-6593-3237 Gündüz Cumhur EGE UNIVERSITY https://orcid.org/0000-0002-4016-0522 Uyanıkgil Yiğit EGE UNIVERSITY 09 30 2022 29 3 324 334 02 27 2022 07 26 2022 Copyright © 1994, Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 1994 Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

AmaçOrgan nakli sonrası mezenkimal kök hücrelerin (MKH)immünosupresif ilaçlarla birlikte kullanımı klinik uygulamalardadikkat çekici hale gelmektedir. Bununlabirlikte, ilaçlar MKH'leri olumsuz yönde etkilemektedir.Antioksidan bir molekül olan ursodeoksikolik asit(UDKA) bu etkileri tersine çevirebilecektir. Bu çalışmanınamacı, sirolimus ve UDKA'nın bireysel ve kombinasyonolarak uygulanmasının insan yağ dokusukaynaklı MKH'ler (YDKMKH) üzerindeki etkilerininincelenmesidir.Gereç ve YöntemEtken maddelerin sitotoksik etkileri zamana ve dozabağlı WST-1 testi ile değerlendirildi. Kombinasyonetkileri, izobologram analizi kullanılarak belirlendi.Apoptoz ve hücre döngüsünün değerlendirilmesi içinMuse hücre analizörü kullanıldı. Oksidatif stress belirteçlerinindeğişimi biyokimyasal yöntemle ölçüldü.BulgularSirolimusun IC50 dozu 48. saatte 18.58μM olarakbelirlendi. UDKA uygulanan doz aralığında sitotoksiketki belirlenmediği için apoptoz, hücre döngüsü veoksidatif stres indikatör analizlerine 100 μM güvenlidoz ile devam edildi. Sirolimusun, apoptozu teşvik ettiğive hücre proliferasyonunu inhibe ettiği belirlendi.UDKA'nın antioksidan özelliği ile sirolimusun YDKMKH'lerüzerindeki apoptotik ve antiproliferatif etkileriniazalttığı belirlendi.SonuçOrgan ve doku transplantasyonu sonrası immünosupresiftedavi ile kombinasyon halinde UDKA tedavisininYDKMKH'ler üzerinde olumlu etkileri olabilecektir.

ObjectiveThe usage of mesenchymal stem cells (MSC) withimmunosuppressive drugs after organ transplantationis becoming remarkable in clinical applications.However, the drugs negatively affect MSCs.Ursodeoxycholic acid (UDCA), which is an antioxidantmolecule, may reverse these effects. The study aimsthat to determine the effects of sirolimus and UDCAon human adipose tissue-derived MSCs (ADMSCs)individually and in combination.Material and MethodThe cytotoxicity of the agents was evaluated byWST-1 test in time and dose-dependent manner.The combinational effects were determined usingisobologram analysis. Muse cell analyzer was used forthe evaluation of apoptosis and cell cycle. Oxidativestress markers were measured by biochemical methods.ResultsIC50 dose of sirolimus was determined as 18.58μMin the 48th hour. Because no cytotoxic effect wasobserved at the studied doses of UDCA, the apoptosis,cell cycle, and oxidative stress indicator analyseswere continued with a safe dose of 100 μM. Sirolimuspromoted apoptosis and inhibited cell proliferation.It was determined that UDCA reduced the apoptoticand anti-proliferative effects of sirolimus on ADMSCswith its anti-oxidant property.ConclusionThe UDCA treatment in combination withimmunosuppressive therapy after organ and tissuetransplantation may have positive effects on ADMSCs.

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