What does this research mean for the field?

Exosomal miR-223-3p from adipose-derived stem cells alleviates hypoxia/reoxygenation-induced ferroptosis in cardiomyocytes by targeting and inhibiting the transferrin receptor (TFRC). Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 3, 2026Open Access

Exosomal MiR-223-3p from Adipose-Derived Stem Cells Alleviates Hypoxia/Reoxygenation-Induced Ferroptosis of H9c2 Cells by Inhibiting TFRC

Key Points

Exosomal miR-223-3p increases cell viability and reduces ferroptosis in H9c2 cells after hypoxia/reoxygenation.
Key metrics indicate that exosomal treatment significantly decreased reactive oxygen species and malondialdehyde levels.

Structured PICO

Does exosomal miR-223-3p from ADSCs alleviate hypoxia/reoxygenation-induced ferroptosis in H9c2 cells?

Population

H9c2 cells subjected to hypoxia/reoxygenation (H/R) injury

Intervention

Exosomal miR-223-3p from adipose-derived stem cells (ADSCs)

Outcome

Cell viability, apoptosis, and ferroptosis markers (ROS, MDA, Fe2+, GSH, GPX4, ACSL4, TFRC)surrogate

Exosomal miR-223-3p from adipose-derived stem cells protects against myocardial ischemia-reperfusion injury in vitro by inhibiting TFRC-mediated ferroptosis.

Abstract

Myocardial ischemia-reperfusion injury (MI/RI) refers to the deterioration of cardiac function after restoring ischemic myocardium perfusion. Stem cell exosomes have produced unique advantages in treating MI/RI. However, the roles of exosomal microRNA-223-3p (miR-223-3p) from adipose-derived stem cells (ADSCs) on MI/RI are still unclear. This study aimed to investigate the effects of exosomal miR-223-3p from ADSCs on hypoxia/reoxygenation (H/R)-induced H9c2 cell injuries. Our findings indicated that the separated ADSC-derived exosomes (ADSC-Exo) were spherical, with a complete cell membrane, an average diameter of 110 nm, and CD9 and CD63 expression. ADSC-Exo increased the cell viability, proliferation, glutathione (GSH) level, and glutathione peroxidase 4 (GPX4) and miR-223-3p expression and decreased the apoptosis, reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+ levels and acyl-CoA synthetase long chain family member 4 (ACSL4) and transferrin receptor (TFRC) expression of H9c2 cells. Overexpressing exosomal miR-223-3p from ADSCs further strengthened the effects of ADSC-Exo on H9c2 cells. Overexpressing TFRC in H9c2 cells effectively reversed the effects of miR-223-3p overexpressed ADSC-Exo on H9c2 cells. In addition, miR-223-3p targeted and negatively regulated TFRC. This study confirmed that exosomal miR-223-3p from ADSCs alleviated H/R-induced ferroptosis of H9c2 cells by inhibiting TFRC, providing a novel target and pathway for the clinical treatment of MI/RI.

Bookmark

View Full Paper