# Functional characterization of Bone-Marrow EPC derived exosomes

> **NIH NIH P01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $457,230

## Abstract

Available evidence from pre-clinical and clinical studies indicates that adult autologous stem cell based
therapies show modest improvement of cardiac function. Emerging evidence from preclinical studies
also suggests that hostile micro-environment in the infarcted myocardium, including inflammation and
oxidative damage, have adverse effects on transplanted stem cell survival and function thereby posing a
significant barrier to the adult stem cell-based therapies for repair of injured myocardium. Therefore,
novel approaches to enhance full functional benefits of stem cell based therapies are critically needed.
Therefore use of cell-free components derived from stem cells including need to be explored for their
reparative potential. Exosomes derived from number of stem cells may provide one such cell-free
source. Exosomes, known regulators of intercellular communication, carry the cell specific mRNA/miRNA
signature and participate in cell-cell communication by transferring their materials to the target cells.
However, both the content and function of the exosome, even from the same cell source, may differ in
context of cellular stresses such as diabetes and inflammation, known co-morbid factors in heart disease
patients, a hypothesis supported by our key preliminary data on endothelial progenitor cell (EPC)
exosomes. Our central hypothesis is that stress conditions of inflammation and hyperglycemia
suppress reparative properties of EPC/stem cell exosomes and this loss of function is dependent upon
stimulus-specific modifications in the exosomal miRNA/protein contents and their delivery to target
cell/tissue. We will test our central hypothesis by conducting experiments organized under following 3
specific aims: 1) Elucidate stimulus-mediated impairment in myocardial reparative ability of EPC-derived
exosomes in ischemic myocardial repair and identify the molecular determinants for exosome
dysfunction; 2) To establish the role of selected microRNAs and signaling proteins as determinants of
exosome dysfunction in response to stress stimuli and determine if their modulation rescues exosome
phenotype; and 3) To determine the therapeutic potential of Human CD34 derived exosomes for post
injury myocardial repair in clinically relevant large animal (swine) model of ischemia-reperfusion. The
significance of this study is to develop a novel understanding of the role played by stem cell/EPC
exosomes in supporting endogenous reparative processes in the heart. We will also extend these studies
to determine the contribution of stimulus-specific miRNAs in regulating EPC-exosome reparative
response to pathologic injury. Establishing the therapeutic value of these exosomes would help develop
a novel cell free system to enhance myocardial repair and would provide a new direction for the
restoration and/or augmentation of endogenous myocardial repair process.

## Key facts

- **NIH application ID:** 9980468
- **Project number:** 5P01HL134608-04
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Raj Kishore
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $457,230
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980468

## Citation

> US National Institutes of Health, RePORTER application 9980468, Functional characterization of Bone-Marrow EPC derived exosomes (5P01HL134608-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980468. Licensed CC0.

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