# Exosomes from miR-primed endothelial progenitor cells for treating ischemic stroke

> **NIH NIH R01** · MARSHALL UNIVERSITY · 2022 · $323,750

## Abstract

Project Summary
Ischemic stroke (IS), loss of cerebral blood flow due to occlusion of cerebral blood vessels, remains one of the
most severe health problems in the world. Current treatments for stroke, such as thrombolytic agents, PTAS,
and neuroprotective drugs have shown to be helpful; however, they are also limited by a narrow therapeutic time
window, risk of re-stroke and low effectives. Looking for an ideal therapeutic strategy that protect brain from
acute injury and promote angiogenesis and neurogenesis for neurological functional recovery, is thus imperative
needed. Endothelial progenitor cells (EPCs) with the ability to differentiate into mature endothelial cells (ECs),
are known to participate in angiogenesis and neurogenesis. EPC transplantation has shown promising results
for IS therapy. Emerging evidence suggests that stem cell released EXs could be used for treating IS. EXs are
endosomal origin small-membrane vesicles mediating cell-cell communication by transferring miRNAs (miRs).
Stem cell EXs hold advantages over stem cells because of lacking self-proliferation and are easier to store and
deliver than cells. In this project, we aim to use EPC-released EXs (EPC-EXs) as a novel avenue for IS therapy
as they selectively carry enriched miR-126. We have found that EPC-EXs protect ECs from
hypoxia/reoxygenation (H/R)-induced injury and dysfunction mainly through their carried miR-126; transfusion of
EPC-EXs could preserve cerebral blood flow (CBF) and decrease infarct volume after IS. Of interest, the anti-
apoptosis/anti-oxidative stress miR-210 has been found to be decreased in the stroke patients. We discovered
that miR-210 primed EPC-EXs (EPC-EXsmiR210) are more effective than EPC-EXs in protecting ECs from H/R-
induced injury. Taken together, by combining the beneficial effects of EPCs (stem cells), EXs (novel player of
brain microenvironment), and miRs (multiple signaling pathway targets), we believe that EPC-EXsmiR210 could
serve as a novel therapeutic avenue for IS. Three aims are designed to test our hypothesis that EPC-EXsmiR210
have enhanced therapeutic effects on IS by protecting brain cells from acute ischemic injury and promoting
angiogenesis/neurogenesis for neurological functional recovery through EPC-EXs, miR-126 and miR-210
downstream pathways, VEGF/VEGFR2/PI3K/Akt, PIK3R2/PI3K/Caspase and BDNF/TrkB/PI3K/Akt. Aim 1:
Determine whether EPC-EXsmiR210 have enhanced effects on protecting ECs and neurons from H/R-induced
injury/dysfunction by targeting multiple pathways. Aim 2: Determine whether EPC-EXsmiR210 exert enhanced
effects on protecting brain from IS-induced acute damage by targeting multiple pathways. Aim 3: Determine
whether EPC-EXsmiR210 exert enhanced effects on promoting neurovascular genesis and functional recovery after
IS by targeting multiple pathways.
.

## Key facts

- **NIH application ID:** 10356178
- **Project number:** 5R01NS102720-05
- **Recipient organization:** MARSHALL UNIVERSITY
- **Principal Investigator:** Ji Chen Bihl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $323,750
- **Award type:** 5
- **Project period:** 2018-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356178

## Citation

> US National Institutes of Health, RePORTER application 10356178, Exosomes from miR-primed endothelial progenitor cells for treating ischemic stroke (5R01NS102720-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10356178. Licensed CC0.

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