Mechanism of adipose-derived mesenchymal stem cell exosomes in the treatment of heart failure

Abstract

BACKGROUND Heart failure (HF) is a global health problem characterized by impaired heart function. Cardiac remodeling and cell death contribute to the development of HF. Although treatments such as digoxin and angiotensin receptor blocker drugs have been used, their effectiveness in reducing mortality is uncertain. Researchers are exploring the use of adipose-derived mesenchymal stem cell (ADMSC) exosomes (Exos) as a potential therapy for HF. These vesicles, secreted by cells, may aid in tissue repair and regulation of inflammation and immune responses. However, further investigation is needed to understand the specific role of these vesicles in HF treatment. AIM To investigate the mechanism of extracellular vesicles produced by ADMSC s in the treatment of HF. METHODS Exogenous surface markers of ADMSCs were found, and ADMSCs were cultured. RESULTS The identification of surface markers showed that the surface markers CD44 and CD29 of adipose-derived stem cells (ADSCs) were well expressed, while the surface markers CD45 and CD34 of ADSCs were negative, so the cultured cells were considered ADSCs. Western blotting detected the Exo surface marker protein, which expressed CD63 protein but did not express calnexin protein, indicating that ADSC-derived Exos were successfully extracted. CONCLUSION The secretion of MSCs from adipose tissue can increase ATP levels, block cardiomyocyte apoptosis, and enhance the heart function of animals susceptible to HF. The inhibition of Bax, caspase-3 and p53 protein expression may be related to this process.

Evolving Strategies for Extracellular Vesicles as Future Cardiac Therapeutics: From Macro- to Nano-Applications

“…Serum levels of atrial natriuretic peptide (ANP), which indicate HF progression, were substantially lowered by AD-MSC-EV priming. Additionally, there was a significant decrease in pro-apoptotic markers such as Bax, Caspase-3, and p53 in the cardiac tissue [ 85 ]. Likewise, rat AD-MSC-EVs administered to a rat model of AMI counteracted myocardial fibrosis, improved cardiac function, and promoted macrophage skewing towards the pro-resolving M2 phenotype.…”

“…Rat BM-MSC-EVsModel of cardiac hypertrophy onH9c2 cells: ⬇ Bax, Caspase-3 ⬆ Bcl-2 ⬇ BNP, TNF-α ⬇ IL-1β, IL-4, IL-6[73,74] Human AD-MSC-EVsModel of cardiac hypertrophy withiPSC-CM: ⬇ ANF, COL1A1, IL-6[77] MurineAD-MSC-EVsRat model of Doxorubicin-induced HF:⬆ ATP content, EF, FS ⬇ ANP, Bax, Caspase-3, p53[85] Rat AD-MSC-EVs Rat model of AMI: ⬆ Cardiac function M2 macrophage transition ⬇ IL-6, IL-1β, IFN-γ, TNF-α[77] …”