Grant Award Details

Exosomal Y-RNAs as mediators of bioactivity of cardiac-derived cell therapy
Grant Number: 
Project Objective: 
  • To explore the contribution of a class of small non-coding RNAs, the Y-RNAs, which are enriched in exosomes (exo) secreted from cardiosphere-derived cells (CDCs). 

Disease Focus: 
Heart Disease
Human Stem Cell Use: 
Adult Stem Cell
Award Value: 

Progress Reports

Reporting Period: 
Year 1

Grant Application Details

Application Title: 
  • Exosomal Y-RNAs as mediators of bioactivity of cardiac-derived cell therapy
Public Abstract: 

Research Objective

We propose to dissect the contribution of Y-RNAs, small non-coding RNA species enriched in CDC-exosomes, in mediating the effect of CDC-exosomes on cardioprotection and macrophage polarization.


Examining the contribution of highly represented RNA species in CDC-exo could allow a better understanding of the mechanism of action of CDC-exo and modulation of their cargo to enhance their potency.

Major Proposed Activities

  • Epigenetic reprogramming.
    Effect of Y-RNA on the heritable changes in gene activity and expression that occur without alteration in DNA sequence, which could explain the sustained effects of CDC-exo.
  • Cardioprotective role of Y-RNA is correlated with macrophage polarization.
    In vitro analyses of the anti-inflammatory pathway mediated by Y-RNA (IL10, anti-inflammatory cytokine, increase by Y-RNA).
  • Structural analyses of Y-RNA fragment.
    Generation of mutated fragments resulting in a change in the secondary structure that could affect the function.
  • Functional analyses of the Y-RNA/hnRNPH1 complex in crucial aspects of RNA processing (pre-mRNA splicing...) in normal and pathological conditions.
Statement of Benefit to California: 

About 610,000 people, men and women, die each year from heart disease in the US (1 in every 4 deaths), motivating the development of more effective therapeutic strategies.

We propose to characterize the implication of Y-RNA, highly enriched in CDC-exosomes, in mediating cardioprotection following a heart attack. This characterization will allow a safe modulation of exosomal RNA content, opening up the possibility that exosomes may become next-generation off-the-shelf therapeutic products.