Blocking Nox2 improves mesenchymal stem cells therapy in myocardial infarction via antagonizing oxidant and promoting...

Area of Science:

• Stem Cell Biology
• Oxidative Stress
• Cardiovascular Research

Background:

• Reactive oxygen species (ROS) contribute to aging and apoptosis in bone marrow-derived mesenchymal stem cells (BMSCs).
• NADPH oxidase 2 (Nox2) is a significant source of intracellular ROS.
• BMSCs are crucial for treating conditions like myocardial infarction (MI).

Purpose of the Study:

• To investigate if inhibiting Nox2 enhances BMSC resilience against oxidative stress, aging, and apoptosis.
• To evaluate the impact of Nox2 inhibition on the therapeutic potential of BMSCs in myocardial infarction.

Main Methods:

• Nox2 was inhibited in BMSCs using Acetovanillone (Nox2 inhibitor) and Nox2 siRNA.
• Cell viability, apoptosis, senescence, and survival were assessed using CCK-8, Edu staining, TUNEL, β-galactosidase assays, and DAPI labeling.
• In vivo studies involved assessing cardiac function (EF, FS) and BMSC retention in a myocardial infarction model.

Main Results:

• Nox2 inhibition significantly countered H₂O₂-induced decreases in BMSC viability and increases in aging and apoptosis.
• Nox2 overexpression worsened BMSC viability reduction, senescence, and apoptosis, while ROS accumulation was suppressed by Nox2 blocking.
• In vivo, Nox2 knockdown in grafted BMSCs improved cardiac function and increased BMSC survival and retention in infarcted myocardium.

Conclusions:

• Inhibiting Nox2 enhances the anti-aging and anti-apoptotic capabilities of BMSCs under oxidative stress.
• Nox2 inhibition promotes BMSC survival and retention, offering a novel strategy to improve BMSC-based therapies.
• This approach holds promise for enhancing the efficacy of stem cell therapy for myocardial infarction.