Large and small extracellular vesicles from Wharton's jelly MSCs: Biophysics, function, and strategies to improve immunomodulation

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Extracellular vesicles (EVs) have emerged as mediators of immunosuppression and pro-regenerative processes, particularly through mesenchymal stromal cells (MSCs) across various disease models. Despite significant progress, there is still a need for a deeper understanding of EV content and functionality to fully harness their biomedical potential. Moreover, strategies to enhance EV production for clinical scalability are still under development. This study aimed to characterize two distinct types of EV-large EV (lgEV) and small EV (smEV)-secreted by Wharton's jelly MSCs (WJ-MSCs). Strategies were explored to augment both EV production and their immunoregulatory effects. Both lgEV and smEV displayed typical EV markers and demonstrated inhibition of human lymphocyte proliferation. Furthermore, analysis of IsomiR content revealed a pronounced immunomodulating signature within MSC-derived EVs, validated by a dual-fluorescence reporter system. MSC primed with pro-inflammatory cytokines yielded increased production of lgEV and smEV, enhancing their immunomodulatory potency. Finally, genetically engineering WJ-MSC to express CD9 resulted in lgEV and smEV with heightened efficacy in suppressing lymphocyte proliferation. This study successfully isolated, characterized, and demonstrated the potent immunosuppressive effect of WJ-MSC-derived lgEV and smEV. We propose cytokine preconditionin

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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