Studies on the effects of bone marrow stem cells on mitochondrial function and the alleviation of ARDS

Abstract

Mesenchymal stem cells (MSCs) can alleviate acute respiratory distress syndrome (ARDS), but the mechanisms involved are unclear, especially about their specific effects on cellular mitochondrial respiratory function. Thirty mice were allocated into the Control, LPS, and LPS + Bone marrow mesenchymal stem cell (BMSC) group (n = 10/group). Mouse alveolar epithelial cells (MLE-12) and macrophage cells (RAW264.7) were divided into the same groups. Pathological variation, inflammationrelated factors, reactive oxygen species (ROS), ATP levels, and oxygen consumption rate (OCR) were analyzed. Pathologic features of ARDS were observed in the LPS group and were significantly alleviated by BMSCs. The trend in inflammationrelated factors among the three groups was the LPS group > LPS + BMSC group > Control group. In the MLE-12 co-culture system, IL-6 was increased in the LPS group but not significantly reduced in the LPS + BMSC group. In the RAW264.7 co-culture system, IL-1β, TNF-α, and IL-10 levels were all increased in the LPS group, IL-1β and TNF-α levels were reduced by BMSCs, while IL-10 level kept increasing. ROS and ATP levels were increased and decreased respectively in both MLE-12 and RAW264.7 cells in the LPS groups but reversed by BMSCs. Basal OCR, ATP-linked OCR, and maximal OCR were lower in the LPS groups. Impaired basal OCR and ATP-linked OCR in MLE-12 cells were partially restored by BMSCs, while impaired basal OCR and maximal OCR in RAW264.7 cells were restored by BMSCs. BMSCs improved the mitochondrial respiration dysfunction of macrophages and alveolar epithelial cells induced by LPS, alleviated lung tissue injury, and inflammatory response in a mouse model of ARDS.

Bone mesenchymal stem cell extracellular vesicles delivered miR let-7-5p alleviate endothelial glycocalyx degradation and leakage via targeting ABL2

“…These findings clarified the effectiveness of bMSCs cell therapy on LPS-induced EG degradation and implied that the related mechanism may be associated with inflammation regulation.bMSCs are known for their considerable immunomodulatory functions, a meta-analysis showed that bMSCs attenuated circulating inflammatory cytokine levels and protected against organ injury in animal studies [ 33 ]. Several laboratory studies have shown that MSCs reduce pulmonary edema by regulating calcium signaling pathways, and focal adhesion between ECs [ 19 , 40 ]. The modalities and targets of inflammation modulation of bMSCs in LPS-induced EG degradation and leakage are elucidated in the present study.…”

Role of biomarkers and molecular signaling pathways in acute lung injury

“…They are rendered toxic as they damage lipids, proteins, and DNA and can represent themselves as damage-associated molecular patterns (DAMPs) that promote inflammation and tissue injury [89,90]. During lung infection, neutrophils generate large amounts of ROS via the NADPH oxidase (NOX) complex [91,92]. The activation of the NOX enzyme complex is the process by which bacteria cause excessive ROS production in neutrophils.…”