Abstract 18996: Exosomes Derived From Cortical Bone Stem Cells Are a Novel Cardioprotective Therapy < Myocardial Injury
Rationale: Cortical bone derived stem cells (CBSCs) have gained prominence recently due to their incredible growth kinetics and myocardial repair properties that outperform known stem cell types used for cardiac repair. Salutary effects of CBSCs in large are mediated by paracrine secretion. Since exosomes represent active component of released factors whether CBSC derived exosomes (CBSCs-Exo) are a viable therapy for heart repair after injury is presently unknown.
Objective: Determine the therapeutic value of CBSC exosomes and their contents for myocardial repair.
Methods and Results: Exosomes isolated from murine CBSCs by ultracentrifugation showed typical exosome size (30-100nm) validated by electron microscopy and dynamic light scattering. To determine cardiac therapeutic value, CBSC exosomes (60μg) injected mice after myocardial infarction (MI) demonstrated reduced infarct size and increased myocyte protection after acute MI injury. Interestingly, serum levels of pro-inflammatory cytokines were significantly reduced along with decreased expression of CD68+ cells in animals receiving CBSCs-Exo versus control animals. Long term analysis of CBSC-Exo animals showed improved cardiac function and contractility compared to saline treated animals concurrent with enhanced angiogenesis 6 weeks after MI. Salutary effects of CBSC-Exo were confirmed in vitro and showed increased cardiac protection in NRVMs after hypoxic challenge and enhanced tube formation in HUVECs. Simultaneously, treatment of bone marrow-derived macrophages stimulated with lipopolysaccharide (LPS) and treated with CBSCs-Exo showed increased polarization towards M2 phenotype demonstrating immunomodulation capacity of CBSC-Exo. The underlying mechanism for beneficial effects was tied to increased packaging of cardioprotective miRs in CBSCs-Exo confirmed by MiRNA array analysis.
Conclusion: Exosomes derived from CBSCs provide a cell free system using reparative power of CBSC to augment cardiac function after myocardial injury recapitulating earlier findings with CBSCs. Increased packaging of cardioprotective and immune-modulatory miRs highlight a potential new insight into the salutary effects of exosome therapy.
- Stem/progenitor cells
- Myocardial infarction
- Inflammation and inflammatory markers
Author Disclosures: S. Mohsin: None. C.D. Troupes: None. D.M. Eaton: None. M. Khan: None. X. Fan: None. J. Johnson: None. E.A. Feldsott: None. Y. Yang: None. T. Wang: None. H. Kubo: None. R.M. Berretta: None. S.R. Houser: None.
- © 2016 by American Heart Association, Inc.