Research articles
ScienceAsia 52 (2026): 1-12 |doi:
10.2306/scienceasia1513-1874.2026.083
hUMSC-sEVs protect the heart against ischemia/reperfusion
injury by delivering circRNA to inhibit ferroptosis
Yang Zhoua,?, Qing-Lei Longb,c,?, Ling Wanga, Yu-Jie Yanga, Yue Wangb,d,e,*, Xiang-Qun Yanga,*
ABSTRACT: Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hUMSC-sEVs) have
been shown to protect against myocardial ischemia/reperfusion (I/R) injury; however, whether they can alleviate
cellular ferroptosis in this process and the underlying molecular mechanisms remain unclear. Our results showed that
hUMSC-sEVs reduced infarct size, improved cardiac function, and inhibited cardiomyocyte ferroptosis in mice. Our
study screened for functionally active circular RNAs (circRNAs) in hUMSC-sEVs and microRNAs (miRNAs) with altered
expression following myocardial I/R via sequencing and further validated the targeted binding interaction between
has_circ_0049673_STX10 (circSTX10) and miR-490-3p through integrated bioinformatics prediction. Overexpression
of circSTX10 in HL-1 cardiomyocytes alleviated miR-490-3p-induced ferroptosis, characterized by reduced ferrous
iron accumulation, suppressed lipid peroxidation, and reversed downregulation of GPX4 expression. Our results
showed that miR-490-3p was upregulated in the I/Rmodelandpromotedcardiomyocyteferroptosis by downregulating
hephaestin-like 1 (Hephl1), which induces intracellular ferrous iron accumulation and lipid peroxidation. Collectively,
this study revealed a novel mechanism whereby hUMSC-sEVs inhibit myocardial I/R injury via circSTX10 binding to
miR-490-3p, thereby exerting cardioprotection against cardiomyocyte ferroptosis, which offers new insights into the
development of therapeutic strategies for this injury.
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| a |
Department of Human Anatomy, School of Basic Medicine, Naval Medical University, Shanghai 200433 China |
| b |
Department of Stem Cell and Regeneration Medicine, Translational Medicine Research Center, Naval Medical
University, Shanghai 200433 China |
| c |
Department of Histology and Embryology, Basic Medicine College, Naval Medical University,
Shanghai 200433 China |
| d |
Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200120 China |
| e |
Shanghai Key Laboratory of Cell Engineering, Shanghai 200025 China |
* Corresponding author, E-mail: wangyuesmmu@163.com, yangxqsmmu@126.com
Received 8 Feb 2026, Accepted 5 Aug 2026
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