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Poor viability of engrafted stem cells hampers therapeutic efficacy for treatment of myocardial infarction (MI). This study is to investigate the role of Inositol phosphates 6 kinase (IP6Ks) for improving mesenchymal stem cells (MSCs) functional survival and cardiac protective effects after transplantation into infarcted mice hearts.
Methods and results
Bone marrow derived MSCs, isolated from dual-reporter firefly luciferase and enhanced GFP positive (Fluc+-eGFP+) transgenic mice, were preconditioned with IP6Ks inhibitor TNP (0.5µmol/L, 1µmol/L, 5µmol/L, 10µmol/L) for 2 h followed by 6 h of hypoxia and serum deprivation (H/SD) injury. TNP at 10μM significantly decreased IP7 production with increased Akt phosphorylation. Moreover, TNP (10μM) improved the viability and enhanced the paracrine effect of MSCs after H/SD. Furthermore, MSCs were transplanted into infarcted hearts with or without selective IP6Ks inhibition. Longitudinal bioluminescence imaging and immuno-staining revealed that TNP pretreatment enhanced survival of engrafted MSCs, which overtly promoted the anti-apoptotic and pro-angiogenic efficacy of MSCs in vivo. Furthermore, MSCs therapy with IP6Ks inhibition significantly decreased fibrosis and preserved heart function.
Inhibition of IP6Ks promotes MSCs engraftment and paracrine effect in infarcted hearts by down-regulating IP7 production and enhancing Akt activation, which might attribute to preserved myocardial function after MI.
Poster Sessions, Expo North
Saturday, March 09, 2013, 10:00 a.m.-10:45 a.m.
Session Title: Acute Coronary Syndromes: Basic I
Abstract Category: 2. Acute Coronary Syndromes: Basic
Presentation Number: 1127-188
- 2013 American College of Cardiology Foundation