Exosomes derived from TNF-α-treated bone marrow mesenchymal stem cells ameliorate myocardial infarction injury in mice

Organogenesis. 2024 Dec 31;20(1):2356341. doi: 10.1080/15476278.2024.2356341. Epub 2024 May 20.

Abstract

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) exhibit considerable therapeutic potential for myocardial regeneration. In our investigation, we delved into their impact on various aspects of myocardial infarction (MI), including cardiac function, tissue damage, inflammation, and macrophage polarization in a murine model. We meticulously isolated the exosomes from TNF-α-treated BMSCs and evaluated their therapeutic efficacy in a mouse MI model induced by coronary artery ligation surgery. Our comprehensive analysis, incorporating ultrasound, serum assessment, Western blot, and qRT-PCR, revealed that exosomes from TNF-α-treated BMSCs demonstrated significant therapeutic potential in reducing MI-induced injury. Treatment with these exosomes resulted in improved cardiac function, reduced infarct area, and increased left ventricular wall thickness in MI mice. On a mechanistic level, exosome treatment fostered M2 macrophage polarization while concurrently suppressing M1 polarization. Hence, exosomes derived from TNF-α-treated BMSCs emerge as a promising therapeutic strategy for alleviating MI injury in a mouse model.

Keywords: BMSCs; TNF-α; exosomes; macrophage polarization; myocardial infarction.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Disease Models, Animal
  • Exosomes* / metabolism
  • Macrophages / metabolism
  • Male
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / drug effects
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction* / therapy
  • Tumor Necrosis Factor-alpha* / pharmacology

Substances

  • Tumor Necrosis Factor-alpha

Grants and funding

The study was supported by Hebei Medical Science Research Program (No. 20240119).