Abstract 14690: Microrna-495 Mediates the Angiogenic Potential of iPSC-Derived Endothelial Cells in Infarcted Heart
Background and Objective: miR-495 inhibition is known to enhance mesoderm differentiation, but its role in angiogenesis is not clear. The present study seeks to determine whether miR-495 mediates angiogenesis induced by human induced pluripotent stem cells (hiPSCs) in infarcted heart.
Methods: The miR-495 in hiPSCs was knocked down via lentivirus. ECs were generated from hiPSCs (hiECs) and sorted by MACS using CD144 antibody (Fig. 1A). In vitro: the angiogenic potential of hiECAnti-495 (hiECScr as control) was analyzed by tube formation and expression of angiogenic genes was detected by PCR array. In vivo: hiECs were transplanted into infarcted heart of immunodeficient mice (LAD ligation); after 4 weeks, hearts were harvested for immunostaining and genome PCR to identify implanted cells.
Results: In vitro: The tube length of hiECAnti-495 was increased (Fig. 1B) and multiple angiogenic genes (EFNB2, TIE2, IGF1, and JAG1) were upregulated in hiECAnti-495 as compared to hiECScr (Fig. 1C). In vivo: Implantation of hiECAnti-495 increased the isolectin-B4+capillary density in the infarcted heart (Fig. 1D). hiECAnti-495 integrated into mouse vascular networks, whereas the structural integration of hiECScr was seldom observed. Human DNA derived from hiECAnti-495 in infarcted heart was higher as compared to hiECScr (Fig.1E).
Conclusion: miR-495 represents a promising mediator for promoting angiogenic potential and functional integration of hiPSC-derived ECs for the treatment of infarcted heart.
Author Disclosures: J. Liang: None. W. Huang: None. W. Cai: None. M. Xu: None. C. Paul: None. R. Millard: None. Y. Wang: None.
- © 2015 by American Heart Association, Inc.