Resveratrol maintain human iliac bone marrow mesenchymal stem cells stemness through sirtuin 1 mediated regulation of SRY-box transcription factor 2: An In vitro and In silico study Yahya Chairul1,2, Rohman Mohammad S.3,*, Hidayat Mohammad4, Nugraha Alexander P.5, Rantam Fedik A.6,* 1Doctoral Program of Medical Science, Universitas Brawijaya, Malang, Indonesia 2Blambangan General Hospital, Banyuwangi, Indonesia 3Department of Clinical Cardiology and Vascular Medicine, Universitas Brawijaya Malang/Saiful Anwar General Hospital, Malang, Universitas Brawijaya, Malang, Indonesia 4Department of Orthopedics, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia 5Departement of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia 6Laboratory Virology and Immunology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia *Corresponding Author E-mail: ippoenk@ub.ac.id
Online published on 20 February, 2023. Abstract Sirtuin 1 (Sirt-1) - SRY-Box Transcription Factor 2 (sox2) axis maintains the stemness of human MSCs. Resveratrol may maintain stemness of human iliac bone marrow (BM)-MSCs. The aim of this study to investigate resveratrol effect on sox2 to maintain BM-MSCs stemness through an in silico and in vitro study. BM-MSCs was aspirated from orthopedic patients then, cultured in vitro. The study groups were into a control group, resveratrol group at doses of 0.1 μM and 1 μM. The characterization human iliac BM-MSCs was examined by immunocytochemistry analysis cluster of differentiation (CD)73, CD90, CD105 and CD45. The proliferation of human iliac BM-MSCs in each group was analyzed by MTT assay with various dose of resveratrol 0.01 μM; 0.05 μM; 0.1 μM; 0.5 μM; 1 μM respectively. A molecular docking was done to evaluate the interactions between resveratrol, sirt1 and Sox2 in silico. Resveratrol act as Sirt1 activator with high binding affinity between Sirt1 and Sox2 was -883.9 kcal/mol in silico. BM-MSCs at third, fourth, fifth and sixth sub-cultured with administrated resveratrol at dose 1 μM showed more confluent, less apoptosis and less senescence cells than control group. The characterization of human iliac BM-MSCs at third sub-culture showed that positive expression of CD73, CD90 and CD105 but lack of CD45 expression. There was no significant different of BM-MSCs viability percentage after administration of resveratrol with various doses (p>0.05). Resveratrol has an effect to regulate Sox2 expression that can maintain human illiac BM-MSCs proliferation, self-renewal and stemness in silico and in vitro. Top Keywords Resveratrol, Sox2, Stemness, Human iliac, Bone marrow mesenchymal stem cell. Top |