# Modulating Exosome Cargos and Surfaces for Precision Heart Repair

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2021 · $380,000

## Abstract

It has been established that most of the beneficial effects of transplanted cells are indirect:
injected cells secrete paracrine factors that promote endogenous heart repair. Among those
secreted substances, exosomes are 30-100 nm vesicles secreted by a wide range of cell types
including tumor cells and stem cells. Exosomes can transport microRNAs (miRs) that enable
cells to communicate with neighboring cells to change their behavior. The essential miR cargos
underlying the therapeutic potencies of exosomes have yet to be determined. In addition, unlike
stem cells, exosomes do not have migratory ability therefore local injections are performed to
ensure delivery. However, direction injection into the heart is not trivial, normally requiring open-
chest surgery or sophisticated endomyocardial injection setups such as the NOGA mapping
system. It is crucial to develop techniques to target systemically delivered exosomes to the
heart injury. Our long-term goal is to create exosomes with optimized cargos and surfaces for
precision cardiac repair. In our preliminary studies, we compared cultured cardiac stromal cells
from normal and failing human hearts, and isolated exosomes from these cells. In vitro
experiments and animal studies indicate an impaired regenerative activity of exosomes from
heart failure patients. In addition, miR array revealed dysregulation of miR-21 in heart failure
exosomes. Based on those preliminary results, we hypothesize that: i) there is a loss of
therapeutic properties in exosomes from heart failure and such functional loss is due to
alterations in repertoire miRs such as miR-21; ii) modulating such miR cargos could rescue the
regenerative potential of the diseased exosomes; iii) efficient systemic delivery and injury
targeting can be achieved by exosomal surface modification. Studies proposed in this proposal
are highly significant since they aim to enhance our fundamental understating of mechanisms
underlying exosomes' reparative function but may also pave the way for future clinical
translation.

## Key facts

- **NIH application ID:** 10141288
- **Project number:** 5R01HL146153-03
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Ke Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141288

## Citation

> US National Institutes of Health, RePORTER application 10141288, Modulating Exosome Cargos and Surfaces for Precision Heart Repair (5R01HL146153-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141288. Licensed CC0.

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