Apoptotic bodies derived from hypoxic bone marrow mesenchymal stem cells reverse LPS-induced apoptosis delay in neutrophils

Oct 16, 2025Stem cells translational medicine

Dead cell particles from low-oxygen bone marrow stem cells help speed up delayed death in immune cells caused by bacterial toxin

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Abstract

from hypoxia-induced apoptosis of stem cells reversed LPS-induced delayed neutrophil apoptosis.

Neutrophils can experience delayed apoptosis due to excessive activation, contributing to tissue damage and slower disease recovery.
Stem cell-derived apoptotic bodies (ApoBDs) have immunomodulatory effects but are typically prone to apoptosis in inflammatory environments.
ApoBDs specifically reversed the delayed apoptosis of neutrophils induced by Lipopolysaccharide (LPS) without affecting apoptosis under normal conditions.
The observed effect was linked to neutrophils phagocytosing from ApoBDs, which inhibited the activation of the PI3K-AKT signaling pathway.
In a mouse model of skin wound healing, ApoBDs and their miR-125b-5p content promoted neutrophil apoptosis and facilitated early wound closure.
This indicates that ApoBDs could represent a new therapeutic approach for conditions involving disrupted neutrophil apoptosis.

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Immune system disorders underlie numerous chronic inflammatory diseases. Functional status and normal apoptosis of neutrophils are of great significance in the regulation and outcome of inflammation. Excessive activation and delayed apoptosis of neutrophils can lead to additional tissue damage, which may be an important cause of delayed disease recovery. Stem cells have immunomodulatory effects, but transplanted stem cells are prone to apoptosis in the hypoxic-inflammatory microenvironment. However, the capacity of stem cell-derived apoptotic bodies () to regulate neutrophil functions, along with the specific components and mechanisms involved, is still unclear. Our study revealed that ApoBDs stemming from hypoxia-induced apoptosis in bone marrow mesenchymal stem cells reversed Lipopolysaccharide (LPS)-induced delayed neutrophil apoptosis, without notable effects on neutrophil apoptosis under physiological conditions. This functional shift was attributed to the phagocytosis of within ApoBDs by neutrophils, which inhibited the activation of the PI3K-AKT signaling pathway. In a mouse skin wound healing model, ApoBDs and the miR-125b-5p they contain also promoted neutrophils apoptosis around the wound and early wound closure. In summary, we demonstrated that hypoxia-induced apoptosis of bone marrow mesenchymal stem cells produced ApoBDs by transferring miR-125b-5p to neutrophils to reduce the expression of PI3 Kinase p110α and inhibit the activation of the PI3K-AKT signaling pathway, thereby reversing the delay of neutrophil apoptosis induced by LPS, which may be a novel option for the treatment of diseases associated with abnormalities in neutrophil apoptosis.

Key numbers

2 μg/mL

Reversal

Concentration of used to treat .

8 mm

Wound Closure Rate

Diameter of the full-thickness wound created in the mouse skin model.

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Apoptotic bodies derived from hypoxic bone marrow mesenchymal stem cells reverse LPS-induced apoptosis delay in neutrophils

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