# Characterization of the Cardiac Progenitor Cell Exosomes for Optimal Therapeutics

> **NIH NIH R01** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2022 · $686,112

## Abstract

SUMMARY
The potential of stem cell therapies to restore heart function and promote tissue regeneration in response to
injury is evident by the completed and recruiting clinical trials. However, the beneficial effects in these clinical
trials using adult CPCs ( are modest. We have demonstrated that neonatal CPCs have superior efficacy in
repairing the injured heart compared to aCPCs and recently, revealed that the nCPCs beneficial effect is
mediated by a paracrine mechanism through a secretome. Exosomes derived from various type of stem
cells/progenitor cells have been shown to mediate stem cell-triggered therapeutic effects on the injured heart
through their miRNA cargo. Thus, we hypothesize that HSF1 in nCPCs promotes production of exosomes,
functional exosomal miRNAs cargo, and exosome acquisition to recipient cells. The presence of
therapeutic miRNAs including miR199a, miR590 and miR146a in nCPC exosomes stimulates
cardiomyocyte proliferation and suppresses apoptosis and fibrosis by targeting specific genes leading
to the restoration of cardiac function in the injured heart. To test our hypothesis, we proposed three specific
aims. Aim 1 will elucidate the functional role of HSF1 in exosome biogenesis and exosomal cargo
regulation. We will examine whether HSF1 knockdown in nCPCs will abolish their superior ability in generating
functional EXO and EXO cargos, and if HSF1 overexpression in aCPCs will achieve comparable capability to
that of nCPCs in EXO therapeutic functionality. Aim 2 will identify the major exosome molecular target in
exosome-recipient cardiac cells and determine whether HSF1 is essential for exosome acquisition. We
will identify cellular targets of exosomes and if HSF1 is essential for the retention of donor EXOs. We will examine
whether Homer1, Clic5, TRAF6 and IRAK1 as EXO major molecular targets in cardiac function recovery. Aim 3
will determine whether the therapeutic miRNAs mediate the effect of exosomes and whether further
miRNA enrichment achieves optimal cardiac recovery. We will examine the effects of exosomal miRs-199a,
590, 146a on cardiac recovery.

## Key facts

- **NIH application ID:** 10467907
- **Project number:** 7R01HL141922-04
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Sunjay Kaushal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $686,112
- **Award type:** 7
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467907

## Citation

> US National Institutes of Health, RePORTER application 10467907, Characterization of the Cardiac Progenitor Cell Exosomes for Optimal Therapeutics (7R01HL141922-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10467907. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*