Abstract 11432: Can the Functional Benefits of Cardiac Progenitor Cells Be Equaled by Their Secreted Extracellular Vesicles?
Introduction: Cell-derived extracellular vesicles ([EVs], i.e., exosomes and microparticles) have been reported to mediate the cardioprotective effects of stem cells. However, a head-to-head comparison of their effects with those of the cells from which they derive has not been reported.
Hypothesis: The effects of the EV content of human embryonic stem cell (hESC)-derived cardiac progenitors may be equivalent to those of the parent cells.
Methods: One-hundred and thirty-eight immunodeficient mice underwent permanent coronary artery ligation. Three weeks later, those with an echocardiographically-determined LV ejection fraction ≤ 50% were randomly allocated to receive transcutaneous echo-guided peri-infarct injections of alpha-MEM media (controls; n=11), hESC-derived SSEA-1+ cardiac progenitors (500,000 cells in 30 μL, n=15) or 2.3 million AnnexinV+ EVs released from these cells in an equivalent volume (n=16). EVs were collected from the cell-secreted medium by ultracentrifugation and characterized by flow cytometry and specific markers. Outcomes were assessed after 6 weeks by echocardiography. Hearts were then processed for the assessment of tissue and vascular remodeling. All data were collected and analyzed blindly.
Results: Cardiac progenitors were successfully generated by exposure of the pluripotent ESC to bone morphogenetic protein-2, purified by anti-CD15 immunomagnetic sorting and then cultured on vitronectin for 48 hours after which cells or EVs derived from the same cell batch were injected. After 6 weeks, LVESV [m±SEM] in controls did not significantly differ from the pre-injection value (difference: -2.64 ± 1.54 μL, p=0.12). Conversely, in the cell-treated group, LVESV significantly decreased by -4.20 ± 0.96 μL (p=0.0007). A similar decrease was seen in the EV-treated group: -5.73 ± 1.21 μL (p=0.0003). LV end-diastolic volumes were also equally reduced in mice treated with cells (-4.48 ± 1.47 μL, p=0.009) or EVs (-4.29 ± 1.31 μL, p=0.005) but not in controls (-2.46 ± 1.19 μL, p=NS).
Conclusions: These data support that EVs may be critical mediators of the paracrine effects of cell therapy and, for the sake of streamlining translational processes, deserve to be considered as potential alternatives to stem cell transplantation.
Author Disclosures: N. Renault: None. A. Kervadec: None. H. Toeg: None. X. Loyer: None. H. Nemetalla: None. M. Yin: None. L. Arakélian: None. M. Périer: None. V. Bellamy: None. N. El Harane: None. V. Vanneaux: None. J. Larghero: None. A.A. Hagège: None. C. Boulanger: None. M. Ruel: Research Grant; Modest; Medtronic. Honoraria; Modest; Medtronic. J. Silvestre: None. P. Menasché: None.
- © 2014 by American Heart Association, Inc.