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

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.