Abstract 10293: Exosome-mediated Transfer of Pro-angiogenic miRNAs From Mesenchymal Progenitor Cells to Endothelial Cells: An Important Mechanism for Promoting Angiogenesis
Background: Previously, we demonstrated that concentrated conditioned medium (CdM) of mesenchymal stem cells promoted angiogenesis of human umbilical vein endothelial cells (HUVEC). Angiogenic miRNAs (angio-miRs) are key regulators of angiogenic processes. Here, we documented the secretion of specific angio-miRs from mesenchymal progenitor cells (MPC) and examined the role of exosome-mediated transfer of angio-miRs in angiogenesis.
Methods and Results: CdM were obtained from MPC (CdMMPC) and HUVEC (CdMHUVEC), respectively. (1) CdMMPC exerted potent pro-angiogenic effects. The total tube length in HUVEC treated with CdMMPC (31.3 ± 3.6 mm/14.8 mm2) was significantly longer than CdMHUVEC (15.3 ± 3.4 mm/14.8 mm2). (2) Extracellular miRs, secreted from MPC, transferred into HUVEC. miRs in various CdM were determined by real time PCR. Pro-angio-miRs including miRs-24, 30b, 30c, 296, 378a, 424 and let-7f in CdMMPC were higher in CdMMPC than in CdMHUVEC. Notably, these miRs in CdMMPC were significantly decreased following HUVEC cultured in these medium. Meanwhile, the expression of these miRs in HUVEC was increased significantly by 2-5-fold. (3) Exosomes mediated the transfer of miRs between MPC and HUVEC. The expression of these miRs in CdMMPC was decreased dramatically after MPC were treated by GW4869 (10μM), an exosome release inhibitor. The expression of these miRs was also lower in HUVEC treated with CdMMPC+GW4869 than those treated with CdMMPC. Subsequently, exosomes were isolated from CdMMPC (exoMPC), pre-labeled with PKH-26, and added into HUVEC medium. These exoMPC were quickly internalized by HUVEC and promoted pseudopods during tube formation in a similar manner to CdMMPC. In addition, the expression of angio-miRs mentioned above was significantly increased in HUVEC treated with exoMPC. (4) Proangiogenic effect of exoMPC was related to miRs expression. Modulation of miR-30b by anti-miR-30b or mimic-miR-30b resulted in remarkable loss or increase of the pro-angiogenic effects of exoMPC, respectively.
Conclusion: Exosome-mediated transfer of pro-angiogenic miRs from MPC to HUVEC facilitates the angiogenic processes.
- © 2013 by American Heart Association, Inc.