# Smarter exosomes derived from engineered MSCs promote neo-vascularization

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2021 · $505,044

## Abstract

Project Summary/Abstract
Mesenchymal stem cell (MSC) therapy has shown tremendous promise for enabling heart tissue repair after
ischemic injury. The therapeutic effects of stem cells are mediated by paracrine factors. Several studies illustrate
that exosomes (EXO) derived from stem cells play a critical role in stem cell mediated therapy of ischemic
myocardium via increasing angiogenesis. From the translational perspective, EXO have greater salutary
therapeutic effects than whole cells: EXO have fewer potential adverse effects, less immune rejection, are more
amenable to manipulation, and EXO cargo can be modified by preconditioning or genetic manipulation. GATA-
4, a cardiac transcription factor, promotes cardiac morphogenesis, extends cardiomyocyte (CM) survival and
preserves cardiac function via regulating various bioactive molecules and activating cardiac protective miRs.
Our published data indicate that MSC overexpressing GATA-4 (MSCGATA-4) increase MSC survival, protect native
CM and promote angiogenesis, compared to vector-transfect MSC (MSCnull). EXO derived from EXO derived
from GATA-4 overexpressing GATA-4 (ExoGATA-4) are more efficient than EXO from vector-transfected MSC
(Exonull) in protecting CM from ischemic injury. In our pilot study, ExoGATA-4 are enriched with pro-angiogenic
miRs, which regulate vascularization. ExoGATA-4 downregulate the expression of thrombospondin 1, a well-known
endogenous inhibitor of neovascularization. The overarching goal of this project is to exploit effectiveness of
GATA-4 conferred EXO than the ordinary EXO in repairable effects of ExoGATA-4. Our central hypothesis is
that the ExoGATA-4 are enriched with pro-angiogenic miRs and proteins that are transferred into recipient cells and
active multiple signaling pathways, leading to angiogenesis and cardiac repair. Three Specific Aims are
proposed: Aim 1, to determine the role of miRs carried by EXO in response to GATA-4 transfection. Aim 2, to
demonstrate if the transferred bioactive molecules play a critical role in ExoGATA-4 mediated angiogenesis. Aim
3, to test the hypothesis that EXO derived from GATA-4 overexpressing MSCs are more effective than that from
vector-transfected MSCs in promoting angiogenesis and myocardial regeneration. The proposed studies are
innovative because no previous study has systematically examined the effectiveness of ExoGATA-4, with
particular focus on the efficacy of EXO mediated angiogenesis and ischemic heart repair following systemic
administration. Intravenous injection offers the advantage of enabling repeated treatments without the stress of
repeated intramyocardial injections. The proposed study is highly significant because it will evaluate the
concept that the effectiveness of cellular therapy can be reproduced by cell-free EXO and will explore this new
modality for future clinical application by intravenous administration. This project will be the first systematic effort
aimed at developing a completely new strate...

## Key facts

- **NIH application ID:** 10078974
- **Project number:** 5R01HL140962-04
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Min Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $505,044
- **Award type:** 5
- **Project period:** 2018-03-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10078974

## Citation

> US National Institutes of Health, RePORTER application 10078974, Smarter exosomes derived from engineered MSCs promote neo-vascularization (5R01HL140962-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10078974. Licensed CC0.

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