# Predictive and systems modeling of exosome cargo

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $760,278

## Abstract

Abstract
 Adverse remodeling of the myocardium after myocardial infarction speeds progression to
heart failure. While cell therapy has been met with great enthusiasm, there are numerous
shortcomings that prevent long-term functional improvements. Moreover, these cells come from
diseased individuals and immunogenicity limits most studies to autologous therapy. Finally, it is
widely believed that the main effect of cell therapy is mediated by paracrine effectors and not
the cells themselves.
 Our published studies demonstrate that rat cardiac progenitor cells (CPCs) make
exosomes, and when cells are exposed to hypoxia, exosomes are reparative following
infarction. Moreover, we were able to demonstrate potential pathways using computational and
systems biology. Recently, we have been able to isolate CPCs from pediatric biopsies and
show age-related changes in cell therapy in a model of heart failure. Preliminary studies
demonstrate that these exosomes also vary in function by age and hypoxia. Therefore, the
objective of this proposal is to examine the protective/regenerative capacity of human pediatric
CPC exosomes in rat models of ischemia-reperfusion. Additionally, with a large number of
patient samples from a wide variety of children, we can perform multivariate analysis to examine
the factors that affect various in vivo mechanisms. Factors include patient age, gender, and
exposure to hypoxic conditions. Finally, we will expand our model by looking at reparative
exosomes from other cell types, CD34+ cells, and examine whether mechanisms of hypoxic
exosome function are conserved among different cells.
 Completion of the proposed studies will determine whether hypoxic exosomes are a
beneficial therapy for ischemia-reperfusion injury, as well as determine potential patient factors
that contribute to these responses.

## Key facts

- **NIH application ID:** 9840508
- **Project number:** 5R01HL145644-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Michael E Davis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $760,278
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840508

## Citation

> US National Institutes of Health, RePORTER application 9840508, Predictive and systems modeling of exosome cargo (5R01HL145644-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840508. Licensed CC0.

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