Induced Pluripotent Stem Cell-Derived Conditioned Medium Promotes Endogenous Leukemia Inhibitory Factor to Attenuate Endotoxin-Induced Acute Lung Injury.
Vincent Yi-Fong SuShih-Hwa ChiouWei-Chih ChenWen-Kuang YuHuai-Hsuan WuHao ChenKuang-Yao YangPublished in: International journal of molecular sciences (2021)
The conditioned medium of induced pluripotent stem cells (iPSC-CM) can attenuate neutrophil recruitment and endothelial leakage of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Therefore, we investigated the mechanisms by which iPSC-CM regulate the interaction between neutrophils and the endothelium in ALI. Murine iPSCs (miPSCs) were delivered intravenously to male C57BL/6 mice (8-12 weeks old) 4 h after intratracheal LPS injection. A miPSC-derived conditioned medium (miPSC-CM) was delivered intravenously to mice after intratracheal LPS injection. DMSO-induced HL-60 cells (D-HL-60, neutrophil-like cells) and human umbilical vein endothelial cells (HUVECs) were used as in vitro models to assess the interaction of neutrophils and endothelial cells. miPSC-CM diminished the histopathological changes in the lungs and the neutrophil count in bronchoalveolar lavage fluids of ALI mice. miPSC-CM attenuated the expression of adhesion molecules in the lungs of ALI mice. Human iPSC conditioned medium (hiPSC-CM) reduced the expression of adhesion molecules in a HUVEC and D-HL-60 co-culture after LPS stimulation, which decreased the transendothelial migration (TEM) of D-HL-60. A human angiogenesis factors protein array revealed that leukemia inhibitory factor (LIF) was not detected in the absence of D-HL-60 and hiPSC-CM groups. hiPSC-CM significantly promoted the production of endogenous LIF in in vitro models. Administration of an anti-LIF antibody not only reversed the effect of iPSC-CM in ALI mice, but also blocked the effect of iPSC-CM on neutrophils TEM in in vitro models. However, a controlled IgG had no such effect. Our study demonstrated that iPSC-CM promoted endogenous LIF to inhibit neutrophils TEM and attenuate the severity of sepsis-induced ALI.
Keyphrases
- induced pluripotent stem cells
- endothelial cells
- high glucose
- lps induced
- inflammatory response
- high fat diet induced
- diabetic rats
- poor prognosis
- lipopolysaccharide induced
- vascular endothelial growth factor
- anti inflammatory
- oxidative stress
- staphylococcus aureus
- high throughput
- intensive care unit
- nitric oxide
- metabolic syndrome
- signaling pathway
- type diabetes
- mass spectrometry
- acute myeloid leukemia
- ultrasound guided
- immune response
- escherichia coli
- peripheral blood
- acute kidney injury
- atomic force microscopy
- adipose tissue
- wild type
- stress induced
- septic shock
- wound healing