Abstract 3611: Thymosin Beta-4 (TB4) Enhances Cardiosphere-derived Cardiac Stem Cell (CDC)-mediated Cardioprotection by Promoting CDC Migration and Angiogenesis via Akt Phosphorylation
Background The benefits of cardiosphere-derived cardiac stem cell (CDC) therapy appear to be limited by poor cell survival in the post-ischemic environment. Thymosin beta-4 (TB4), a ubiquitous cell protein, promotes cardioprotection by its prosurvival, anti inflammatory and proangiogenic effects. We hypothesize that coadministration of TB4 with CDCs can improve functional outcomes by enhanced cardioprotection and promotion of angiogenesis.
Methods and Results CDCs were cultured from human cardiac biopsies and pretreated in TB4 (10 μg/mL) overnight. On Western blot, Akt phosphorylation was upregulated in TB4 treated CDCs (Fig a⇓), without altering total Akt levels. TB4 increased CDC Boyden chamber migration by 1.5–1.8 times (p<0.05) in a concentration-dependent manner (maximum effect at 10 μg/mL). The total length of capillary-like tubules formed in matrigel was significantly increased in TB4 treated cells vs. controls (p<0.05, Fig b⇓). Immediately after inducing myocardial infarction (MI) by LAD ligation in immunosuppressed mice, intracardiac injections of 105 CDCs, TB4-pretreated 105 CDCs resuspended in TB4, TB4 only or PBS only were performed. On echocardiography, baseline ejection fraction (EF) and fractional area change (FAC) were similar in all groups; however, at 3 weeks, EF and FAC were preserved in TB4-pretreated CDC group, while both decreased significantly in the 3 control groups (p<0.05, Fig c⇓).
Conclusion TB4 modifies the cellular environment, resulting in enhanced CDC-mediated improvement in cardiac function, possibly through upregulation of proangiogenic pathways, providing a potential avenue for improving cardiac stem cell therapy outcomes.