Small extracellular vesicles enhance the survival of Sca-1+ cardiac stem cells against ROS-induced ischemic-reoxygenation injury in vitro

Radwa A Mehanna ^1,2, Hagar Elkafrawy ^3,4, Marwa M Essawy ^3,5

¹Medical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt. radwa.mehanna@alexmed.edu.eg.
²Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt. radwa.mehanna@alexmed.edu.eg.
³Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.
⁴Medical Biochemistry Department, Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.
⁵Oral Pathology Department, Faculty of Dentistry, Alexandria University, Alexandria, 21500, Egypt.
⁶Biotechnology Department, Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.
⁷Molecular Biology Department, Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.
⁸Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.
⁹Medical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.
¹⁰Histology and Cell Biology Department, Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.
¹¹Human Anatomy and Embryology Department, Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.
¹²Medical Biophysics Department, Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt.

⁰Medical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, 21500, Egypt. radwa.mehanna@alexmed.edu.eg.

Biological Research +

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March 5, 2025

View abstract on PubMed

Summary

Small extracellular vesicles (sEVs) from bone marrow-mesenchymal stem cells (BMMSCs) promote cardiac stem cell (CSC) regeneration after ischemic reperfusion (IR) injury. These miRNA-21-5p-rich sEVs enhance CSC proliferation and survival by reducing oxidative stress and apoptosis.

Area Of Science

Cardiovascular Biology
Regenerative Medicine
Stem Cell Biology

Background

Ischemic reperfusion (IR) injury causes myocardial cell death and heart failure via reactive oxygen species (ROS).
The regenerative capacity of cardiac stem cells (CSCs), particularly Sca1+ CSCs, following IR injury is not well understood.

Purpose Of The Study

To investigate if small extracellular vesicles (sEVs) from bone marrow-mesenchymal stem cells (BMMSCs) can protect Sca-1+/CSCs from IR injury.
To determine if BMMSCs-derived sEVs enhance CSC proliferation and reduce apoptosis in vitro.

Main Methods

An in vitro model of IR injury in Sca-1+/CSCs was created using oxygen-glucose deprivation/reoxygenation (OGD/R).
The effects of BMMSCs-derived sEVs on CSC oxidative stress, proliferation, apoptosis, and cell cycle were analyzed.
The involvement of the PTEN/pAkt/HIF-1α pathway was investigated.

Main Results

BMMSCs-derived sEVs treatment shifted Sca-1+/CSCs from quiescence to proliferation and decreased apoptosis.
sEVs-treated CSCs showed increased cell population in the S phase of the cell cycle.
miRNA-21-5p-rich sEVs reduced oxidative stress and stabilized HIF-1α expression.

Conclusions

BMMSCs-derived sEVs, particularly those rich in miRNA-21-5p, enhance the regenerative potential of Sca-1+/CSCs.
These sEVs promote CSC proliferation, cell cycle progression, and survival while mitigating oxidative stress and apoptosis.
sEVs can serve as a preconditioning tool to boost endogenous CSCs for IR injury recovery.

Keywords:

BMMSCs-derived small extracellular vesicles Cardiac stem cells Ischemia-reperfusion injury PTEN/pAkt/HIF-1α pathway miRNA-21-5p

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