Effects of a recombinant adenovirus expressing human hypoxia-inducible factor 1α double-mutant on the in vitro differentiation of bone marrow mesenchymal stem cells to cardiomyocytes / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of mutant hypoxia-inducible factor-1α (HIF-1α) adenovirus (Adeno-HIF-1α-Ala402-Ala564) on cardiomyocytes (CMCs) differentiation from the mesenchymal stem cells (MSCs) co-cultured with CMCs.</p><p><b>METHODS</b>Following groups were studied HIF-1α group (MSCs + CMCs + Ad-HIF-1α), LacZ group (MSCs + CMCs + Ad-LacZ), Sham group (MSCs + CMCs + PBS) and MSC + HIF-1α Group (MSCs + Ad-HIF-1α). MSCs were co-cultured with myocardial cells in proportion of MSCsCMCs 12, after 24 hours, cells were infect with virus (MOI = 100) or treated with PBS, cardiac troponin (cTnT) expression in MSCs was detected 7 days post infection by immunochemical analysis, mRNA expression of HIF-1α, TGF-β(1), Smad4, NKx2.5, GATA-4 was also detected by RT-PCR.</p><p><b>RESULTS</b>HIF-1α increased MSCs differentiation to myocardial cells (differentiation rate 32.68% ± 6.52% vs. 8.28% ± 0.09% in the LacZ group and 10.25% ± 2.20% in the Sham group and 0.32% ± 0.05% in the MSC group (all P < 0.05 vs. HIF-1α group). mRNA expression of HIF, TGF-β(1), Smad4, NKx2.5 and GATA-4 was also significantly upregulated in HIF-1α group all P < 0.05 vs. Sham group).</p><p><b>CONCLUSION</b>HIF-1α promoted MSCs, co-cultured with myocardial cells, differentiating to cardiomyocytes via upregulating TGF-β(1)/Smad4 signaling pathway.</p>