Enhancing exosome-mediated angiotensin-converting enzyme 2 expression modulation: activation of human Wharton’s jelly mesenchymal stem cells derived exosomes through curcumin and quinine

Abstract

Background: Cell-free therapy utilizes components such as secretomes and exosomes whose properties depend on the cellular environment. This study investigates how altering the microenvironment of human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) with curcumin and quinine affects exosome content, potentially influencing ACE2 expression in Vero and Caco-2 cells. Methods and results: hWJ-MSCs were divided into groups treated with curcumin, quinine, DMSO or culture medium only. Secretomes and exosomes were isolated and analyzed, with exosomes characterized by CD63 marker, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Exosome uptake by Vero and Caco-2 cells was monitored over time, and ACE2 expression was assessed by immunocytochemistry (ICC) and Western blotting. The results of this study demonstrated that exosomes averaged 114.3 nm in size and contained 88 miRNAs, with significant miRNA reductions in exosomes treated with curcumin and quinine. Vero and Caco-2 cells internalized these exosomes within 2.5 h and showed a significant decrease in ACE2 expression when treated with curcumin- or quinine-treated exosomes. This effect was associated with changes in miRNA, including miR-125b-5p in treated exosomes. Exosomes modified with curcumin or quinine significantly downregulated ACE2 expression, suggesting that these compounds may affect miRNA expression or loading, thereby affecting ACE2 protein expression. Conclusion: This study highlights the therapeutic potential of bioactive compounds in modulating ACE2 through exosome-carried biomolecules. These findings suggest a potential therapeutic strategy for condition associated with ACE2 dysregulation and warrant further investigation into molecular mechanism involved.