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Updated: Jan 6, 2026
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
Adipose-derived MSC extracellular vesicles ameliorate sepsis by reprogramming macrophages via miR-21-5p targeting
Guannan Zhou1, Jieqiong Song2, Lizhen Xuan2
1Department of Intensive Care Unit, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Abstract:
Sepsis is a common and life-threatening condition encountered in intensive care units (ICUs). Mesenchymal stromal cells (MSCs) and their small extracellular vesicles (EVs) have emerged as promising nanotherapeutics, particularly in the context of COVID-19. This study evaluates the efficacy and mechanisms of adipose-derived MSC EVs (ADMSC-EVs) in a lipopolysaccharide (LPS)-induced sepsis model. We quantified M2 macrophages and IL-10 in peripheral blood mononuclear cells (PBMCs) from both septic patients and healthy donors. ADMSCs and their EVs were isolated, and EVs were administered to LPS-challenged mice. Macrophage phenotypes in lung tissue were analyzed using flow cytometry and immunofluorescence. The biodistribution of EVs was traced with PKH67 green fluorescent cell linker dye (PKH-67), and the signaling pathways involved in macrophage reprogramming were examined. ADMSC-EVs efficiently entered macrophages, promoted M2 polarization, suppressed inflammation, and improved survival rates in septic mice. Biodistribution studies demonstrated widespread organ accumulation, with notable localization in the lungs, liver, and kidneys. Mechanistically, the EV cargo miR-21-5p targeted Pellino E3 ubiquitin protein ligase 1 (PELI1), driving M2 polarization in vivo, which was accompanied by increased IL-10 levels. These findings position ADMSC-EVs as a viable cell-free therapeutic approach for mitigating LPS-induced sepsis through the delivery of miR-21-5p to PELI1, thereby supporting further development of EV-based immunomodulatory strategies for sepsis management.
Insights
Adipose-derived mesenchymal stromal cell extracellular vesicles (ADMSC-EVs) show promise for treating sepsis. These EVs reprogram macrophages, reduce inflammation, and improve survival in a sepsis model by delivering miR-21-5p.
Area of Science:
- Immunology
- Nanomedicine
- Regenerative Medicine
Background:
- Sepsis is a critical condition often treated in intensive care units (ICUs).
- Mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) are explored as nanotherapeutics.
- Adipose-derived MSC EVs (ADMSC-EVs) are investigated for sepsis treatment.
Purpose of the Study:
- To evaluate the efficacy of ADMSC-EVs in a lipopolysaccharide (LPS)-induced sepsis model.
- To elucidate the mechanisms underlying ADMSC-EVs' therapeutic effects on macrophage polarization and inflammation.
- To assess the potential of ADMSC-EVs as a cell-free therapy for sepsis.
Main Methods:
- ADMSC-EVs were isolated and administered to LPS-challenged mice.
- Macrophage phenotypes were analyzed in lung tissue via flow cytometry and immunofluorescence.
- EV biodistribution was tracked, and molecular pathways (miR-21-5p targeting PELI1) were examined.
Main Results:
- ADMSC-EVs were found to enter macrophages, promoting M2 polarization and suppressing inflammation.
- Septic mice treated with ADMSC-EVs exhibited improved survival rates.
- Biodistribution studies showed significant accumulation of EVs in lungs, liver, and kidneys.
- The EV cargo miR-21-5p was identified as a key mediator, targeting PELI1 to drive M2 polarization and increase IL-10 levels.
Conclusions:
- ADMSC-EVs demonstrate significant therapeutic potential for LPS-induced sepsis.
- The mechanism involves miR-21-5p delivery to PELI1, leading to M2 macrophage polarization and reduced inflammation.
- ADMSC-EVs represent a promising cell-free immunomodulatory strategy for sepsis management.
