Abstract 16280: Intramyocardial Delivery of Extracellular Vesicles Released From Induced Pluripotent Stem Cells Induces Cardiac Repair After Myocardial Infarction
Introduction: Induced pluripotent stem cells (iPSCs) have recently emerged as a promising therapy for cardiac repair. Whether extracellular vesicles (EVs) derived from iPSCs can confer similar benefits remains unclear.
Hypothesis: We hypothesized that injection of iPSC-derived EVs would produce at least similar improvement in cardiac structure and function compared with iPSCs.
Methods: Murine iPSCs were generated using standard protocol and iPSC-EVs were harvested from culture supernatants by sequential centrifugation. Wild-type (C57BL/6) mice underwent a 30-min coronary occlusion followed by reperfusion, and 48 h later received intramyocardial injection of vehicle (PBS, n=14), iPSCs (n=15) or iPSC-EVs (n=13). Echocardiography was performed 4 d prior to coronary occlusion/reperfusion (BSL) and at 48 h and 30 d after injection. Mice were sacrificed at 30 d.
Results: At 48 h after injection, LVEF was significantly and similarly reduced in all groups (Fig). At 30 d after MI, mice injected with iPSC-EVs exhibited significantly greater EF (Fig) compared with vehicle-treated mice. iPSC-EV-injected hearts also showed significantly smaller LVEDV compared with vehicle-treated mice, indicating improved remodeling. Although iPSCs-injected hearts also showed somewhat improved function and structure, several mice in this group grew tumors at myocardial injection sites.
Conclusions: We conclude that intramyocardial injection of iPSC-EVs after a reperfused MI improves LV function and remodeling. The use of iPSC-EVs also averts cardiac tumor formation that was noted in mice after iPSC whole cell injection. These findings support therapeutic potential of iPSC-EVs in patients after MI.
Author Disclosures: G. Cheng: None. M. Adamiak: None. Y. Xuan: None. A. Samanta: None. S. Bobis-Wozowicz: None. M. Girgis: None. O. Wang: None. E. Karnas: None. A. Davani: None. S. Kedracka-Krok: None. M. Sarna: None. R.J. Vincent: None. Y. Yang: None. Z. Madeja: None. E. Zuba-Surma: None. B. Dawn: None.
- © 2015 by American Heart Association, Inc.