Abstract 19422: Newt Exosomes Are Shuttles of Bioactive RNAs and Proteins That Have Signaling Capabilities in Mammalian Systems of Cardiac Repair
Introduction: Adult newts can regenerate amputated cardiac tissue, and whole limbs, without fibrosis, unlike adult mammals which lack such regenerative capacity. Exosomes are nanoparticles which mediate intercellular communication and play a critical role in therapeutic regeneration.
Hypothesis: We have previously shown that exosomes from a newt blastema cells have bioactivity in mammalian models of heart regeneration. We hypothesized that we could identify factors responsible for inducing the observed proliferation and cardiac tissue repair. Thus, we extended our studies into exploring the molecular entities associated with these nanoparticles to identify potential key players involved in the therapeutic effects of exosome-mediated heart repair.
Methods: A1 cells, derived from the amputated limb buds of Notopthalmus viridescense, were expanded in culture and their exosomes isolated for RNA cargo and protein content analyses via RNA-Seq and Mass spectrometry. RNA-Seq was also performed on neonatal rat ventricular myocytes (NRVMs) after A1 exosome treatments to monitor exosome-mediated gene pathway signaling changes.
Results: A1 exosomes have an abundance of mRNAs that encode genes associated with cardiac tissue repair and cellular proliferation such as neuregulin, nerve growth factor and the leptin receptor. Numerous miRNAs and other ncRNAs, many of unknown bioactivity, are also present in high abundance. Additionally, we identified A1 exosome proteins that may contribute to target cell proliferation such as periostin, a protein previously identified to be associated with enhanced cardiac tissue repair following myocardial infarction. The RNA-Seq data of A1 exosome-treated NRVM cells also revealed significant upregulation of PI3K/AKT signaling as well as other proliferation-associated pathways.
Conclusions: Newt A1 blastema cells produce extracellular vesicles that carry therapeutic RNA and protein content and have profound bioactivities on mammalian cells and can stimulate cardiomyocyte proliferation, induce cell cycle gene regulatory networks and convey significant, regenerative functional and structural outcomes in rats with myocardial infarction.
- Myocardial infarction
- Stem cell therapy
- Regenerative medicine stem cells
- Cardiac regeneration
- Signal transduction
Author Disclosures: R.C. Middleton: None. E. Tseliou: None. T.J. Antes: Consultant/Advisory Board; Significant; Capricor Therapeutics, Inc. E. Marbán: Ownership Interest; Significant; Capricor Therapeutics, Inc.. Consultant/Advisory Board; Significant; Capricor Therapeutics, Inc..
- © 2016 by American Heart Association, Inc.