Exosomal Y-RNAs as mediators of bioactivity of cardiac-derived cell therapy

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Grant Award Details

Grant Type:
Inception – Discovery Stage Research Projects
Grant Number:
DISC1-08643
Investigator(s):
Name:
Linda Cambier
Institution:
Cedars-Sinai Medical Center
Type:
PI

Disease Focus:
Heart Disease
Human Stem Cell Use:
Adult or Tissue Stem Cell
Award Value:
$181,063
Status:
Closed

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.

Impact

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.

Publications