In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis

Abstract

Background: Sepsis is a global inflammatory disease that causes death. It has been reported that mesenchymal stem cell (MSC) treatment can attenuate inflammatory and septic symptoms. In this study, we investigated how interactions between neutrophils and human umbilical cord blood (hUCB)-MSCs in the liver of septic mice are involved in mitigating sepsis that is mediated by MSCs. Accordingly, we aimed to determine whether hUCB-MSC application could be an appropriate treatment for sepsis. Methods: To induce septic condition, lipopolysaccharide (LPS) was intraperitoneally (i.p.) injected into mice 24 h after the intravenous (i.v.) injection of saline or hUCB-MSCs. To determine the effect of hUCB-MSCs on the immune response during sepsis, histologic analysis, immunoassays, and two-photon intravital imaging were performed 6 h post-LPS injection. For the survival study, mice were monitored for 6 days after LPS injection. Results: The injection (i.v.) of hUCB-MSCs alleviated the severity of LPS-induced sepsis by increasing IL-10 levels (p < 0.001) and decreasing mortality (p < 0.05) in septic mice. In addition, this significantly reduced the recruitment of neutrophils (p < 0.001) to the liver. In hUCB-MSC-treated condition, we also observed several distinct patterns of dynamic interactions between neutrophils and hUCB-MSCs in the inflamed mouse liver, as well as vigorous interactions between hepatic stellate cells (HSCs or ito cells) and hUCB-MSCs. Interestingly, hUCB-MSCs that originated from humans were not recognized as foreign in the mouse body and consequently did not cause graft rejection. Conclusions: These distinct interaction patterns between innate immune cells and hUCB-MSCs demonstrated that hUCB-MSCs have beneficial effects against LPS-induced sepsis through associations with neutrophils. In addition, the immunomodulatory properties of hUCB-MSCs might enable immune evasion in the host. Taken together, our results suggest the prospects of hUCB-MSCs as a therapeutic tool to inhibit inflammation and alleviate pathological immune responses such as sepsis.

Gingival-Derived Mesenchymal Stem Cells Protect Against Sepsis and Its Complications

“…Sepsis is characterized by an uncontrolled inflammatory response involving inflammatory factors, such as IL-1β and TNF-α, and effector cells, such as neutrophils. 21,22 There is convincing evidence that deleterious activation of neutrophils is a critical reason leading to host tissue injury and organ damage during sepsis. 23 MSCs administration is known to reduce neutrophil content in LPS-induced ALI and sepsis.…”

Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

“…Neutrophils are highly versatile cells with various immune functions, such as inflammation mediation, microbial capture via granular proteins, and repair of sterile wounds ( Kruger et al, 2015 ). In particular, during neuroinflammation, neutrophils participate in the general immune response by signaling to diverse cell types, including endothelial cells, mesenchymal stem cells, lymphocytes, and microglia ( Ahn et al, 2020 ). Recent reports have emphasized the variety of roles neutrophils can play in neuroinflammation, where brain resident cells participate in a coordinated fashion ( Liu et al, 2018 ).…”

A cross‐linked anti‐TNF‐α aptamer for neutralization of TNF‐α‐induced cutaneous Shwartzman phenomenon: A simple and novel approach for improving aptamers' affinity and efficiency

“…This finding suggests that the dosage of TNF‐α blocker is adequate for blocking TNF‐α, and neutrophils recruitment was due to locally injected LPS. In the experimental cutaneous Shwartzman phenomenon, LPS or TNF‐α alone cannot induce skin reactions 7,26 ; however, LPS can causes slight inflammation, and neutrophils recruitment, 36 and this finding was detectable in the group of mice treated with only LPS. TNF causes inflammation when injected at the highest dose (about 160 μg), whereas in our experiment 6 μg of TNF was used.…”