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Background <p>Ischemic reperfusion (IR) generates reactive oxygen species (ROS) that inevitably result in myocardial cell death and heart failure. The regenerative power of cardiac progenitor/stem pools (CSCs), especially the Sca1<sup>+</sup> population, in response to IR injury remains unclear.</p> Methods <p>Our work sought to investigate whether small extracellular vesicles (sEVs) isolated from bone marrow-mesenchymal stem cells (BMMSCs) could rescue CSCs, specifically Sca-1+/CSCs, from IR by increasing their proliferative capacity and limiting their apoptosis in vitro. The Sca-1+/CSCs-IR model was induced by the oxygen-glucose deprivation/reoxygenation method (OGD/R). The effects of treatment with BMMSCs-derived sEVs on oxidative stress, cell proliferation, apoptosis, and cell cycle were assessed. To further test the mechanistic action, we assessed the PTEN/pAkt/HIF-1α pathway.</p> Results <p>Compared to hypoxic untreated CSCs, BMMSCs-derived sEVs-treated cells had shifted from their quiescent to proliferative phase (<i>p</i> &gt; 0.05) and showed decreased apoptosis (<i>p</i> &lt; 0.001). sEVs-treated CSCs were predominately in the S phase (11.8 ± 0.9%) (<i>p</i> &lt; 0.01). We identified an abundance of miRNA-21-5P in BMMSCs. HIF-1α expression was highest in CSCs treated with sEVs (<i>p</i> &lt; 0.05). Moreover, miRNA-21-5p-rich sEVs shifted the redox state, reducing oxidative stress and promoting balance (<i>p</i> &gt; 0.05).</p> Conclusion <p>Conditioning Sca-1+/CSCs, an essential population in the postnatal heart, with sEVs rich in miRNA-21 robustly enhanced the proliferation, and synthesis phase of the cell cycle, and stabilized HIF-1α while alleviating oxidative stress and apoptosis. Such sEVs rich in miRNA-21-5p can be further used as a preconditioning tool to enhance endogenous Sca-1+/CSCs regeneration in response to IR injury.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月5日

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  • Radwa A. Mehanna,
  • Hagar Elkafrawy,
  • Marwa M. Essawy,
  • Samar S. Ibrahim,
  • Ashraf K. Awaad,
  • Nehal A. Khalil,
  • Marwa A. Kholief,
  • Abeer Sallam,
  • Heba A. Hamed,
  • Mona A. Barkat,
  • Mohamed F. ElKady,
  • Eman H. Thabet

摘要

Background

Ischemic reperfusion (IR) generates reactive oxygen species (ROS) that inevitably result in myocardial cell death and heart failure. The regenerative power of cardiac progenitor/stem pools (CSCs), especially the Sca1+ population, in response to IR injury remains unclear.

Methods

Our work sought to investigate whether small extracellular vesicles (sEVs) isolated from bone marrow-mesenchymal stem cells (BMMSCs) could rescue CSCs, specifically Sca-1+/CSCs, from IR by increasing their proliferative capacity and limiting their apoptosis in vitro. The Sca-1+/CSCs-IR model was induced by the oxygen-glucose deprivation/reoxygenation method (OGD/R). The effects of treatment with BMMSCs-derived sEVs on oxidative stress, cell proliferation, apoptosis, and cell cycle were assessed. To further test the mechanistic action, we assessed the PTEN/pAkt/HIF-1α pathway.

Results

Compared to hypoxic untreated CSCs, BMMSCs-derived sEVs-treated cells had shifted from their quiescent to proliferative phase (p > 0.05) and showed decreased apoptosis (p < 0.001). sEVs-treated CSCs were predominately in the S phase (11.8 ± 0.9%) (p < 0.01). We identified an abundance of miRNA-21-5P in BMMSCs. HIF-1α expression was highest in CSCs treated with sEVs (p < 0.05). Moreover, miRNA-21-5p-rich sEVs shifted the redox state, reducing oxidative stress and promoting balance (p > 0.05).

Conclusion

Conditioning Sca-1+/CSCs, an essential population in the postnatal heart, with sEVs rich in miRNA-21 robustly enhanced the proliferation, and synthesis phase of the cell cycle, and stabilized HIF-1α while alleviating oxidative stress and apoptosis. Such sEVs rich in miRNA-21-5p can be further used as a preconditioning tool to enhance endogenous Sca-1+/CSCs regeneration in response to IR injury.