7, 8, 3'‐Trihydroxyflavone protects H/R‐induced apoptosis and induces in vivo growth of human embryonic stem cell‐derived cardiomyocytes

BACKGROUND: Cellular therapy of human embryonic stem cell-derived cardiomyocytes (hES-CMs) holds great promise for regenerating infarcted cardiac tissues. Yet, the major challenge remains as little cells survived after grafting. In this study, we examined whether treating hES-CMs with 7, 8, 3'-Trihydroxyflavone (THF) may improve hES-CMs developments both in vitro and in vivo. METHOD: HES-CMs were differentiated in vitro, and treated with 5 μ59M THF for 24 h. The control hES-CMs were treated with PBS. Possible effect of THF on hES-CM differentiation was assessed by viability and western blot assays. HES-CMs were also treated with hypoxia/reoxygenation (H/R)-condition to induce apoptosis. The effect of THF on rescuing H/R-induced hES-CM apoptosis was assessed by TUNEL and western blot assays. HES-CMs were then grafted into infarcted rat hearts. The effect of THF on promoting in vivo growth of hES-CMs was examined by immunohistochemistry. RESULTS: THF pretreatment did not alter the differentiation process of hES-CMs. Under H/R condition, THF rescued hES-CM apoptosis, activated TrkA and TrkB signaling pathways through phosphorylation and induced VEGF production. In in vivo rat model of myocardial infarction, THF induced the growth of transplanted hES-CMs by promoting Cardiac Troponin I and CD31. CONCLUSION: THF has pro-cardiac effect on hES-CMs by protecting cells from H/R induced apoptosis and promoting in vivo growth of cell transplantation in infarcted hearts. These results may help optimizing the cellular therapy of using human embryonic stem cells to benefiting patients suffered from heart attack. This article is protected by copyright. All rights reserved.