Bone marrow mesenchymal stem cell transplantation protects rats from myocardial infarction by regulating TXNIP/NLRP3 pathway-mediated inflammation and fibrosis

Bone marrow mesenchymal stem cells (BMSCs) may be a promising target in the treatment of myocardial infarction (MI). However, the underlying molecular mechanisms of BMSC therapy remain unclear.

This study sought to evaluate the efficacy of direct intramyocardial transplantation of BMSCs in a mouse model of MI.

Mouse BMSCs were transfected with small interfering RNA or overexpression plasmid targeting TXNIP. The viability, proliferation, and apoptosis of BMSCs after hypoxia treatment were detected by MTT method, EdU analysis, and flow cytometry, respectively. A mouse model of MI was constructed, after which BSMCs were injected intramyocardially immediately. Cardiac ultrasound, HE staining, TUNEL staining and ELISA, IHC analysis, and Western blot were adopted to evaluate the effects of BSMC therapy on cardiac function, myocardial inflammation, and fibrosis in mice.

In vitro experiments reported that ablating TXNIP increased viability and inhibited apoptosis of hypoxia-treated BMSCs while overexpressing TXNIP did the opposite. In vivo results stated that BSMCs improved cardiac function, myocardial inflammation, and fibrosis after MI, which was further improved by silencing TXNIP but reversed by overexpressing TXNIP. Meanwhile, in vivo cell tracking experiments showed that the retained BMSCs in the myocardium decreased after transplantation, and TXNIP depletion promoted the survival of BMSCs in MI mice, whereas TXNIP overexpression did the opposite.

In conclusion, BMSC transplantation improves cardiac function, myocardial inflammation, and fibrosis after MI by regulating the TXNIP/NLRP3 pathway.