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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?

SUBMITTER: Ahn SY

PROVIDER: S-EPMC6998265 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Ahn Sung Yong SY Maeng Yong-Sun YS Kim Yu Rim YR Choe Young Ho YH Hwang Han Sung HS Hyun Young-Min YM

Stem cell research & therapy 20200203 1

<h4>Background</h4>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.<h ...[more]

PMID: 32014040

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Project description:Despite the extensive hepatic differentiation potential of human umbilical cord lining-derived mesenchymal stem cells (hUC-MSC), little is known about the molecular mechanisms of hUC-MSC differentiation. At the post-transcriptional level, microRNAs are key players in the control of cell fate determination during differentiation. In this study, we aimed to identify microRNAs involved in the hepatic differentiation of hUC-MSCs. After successfully isolating hUC- MSCs, we induced hepatocyte formation in vitro with growth factors. After 26 days of induction, hUC-MSCs could express hepatocyte-specific genes, synthesize urea and glycogen and uptake low-density lipoprotein. Cellular total RNA from hUC-MSCs and hepatic differentiated hUC-MSCs was collected at 7 time points, including 2 days, 6 days, 10 days, 14 days, 22 days and 26 days, for microRNA microarray analysis. Dynamic microRNA profiles were identified that did not overlap or only partially overlapped with microRNAs reported to be involved in human liver development, hepatocyte regeneration or hepatic differentiation of liver-derived progenitor cells. A total of 61 microRNAs among 1205 human and 144 human viral microRNAs displayed consistent changes and were altered at least 2-fold between hUC-MSCs and hepatic differentiated hUC-MSCs. Among these microRNAs, 25 were over-expressed; this over-expression occurred either gradually or increased sharply and was maintained at a high level. A total of 36 microRNAs were under-expressed, with an expression pattern similar to that of the over-expressed microRNAs. The expression of the altered expressed microRNAs was also confirmed by quantitative reverse-transcription polymerase chain reaction. We also found that microRNAs involved in hepatic differentiation were not enriched in hepatocyte or hepatocellular carcinoma cells and can potentially target liver-enriched transcription factors and genes. The elucidation of the microRNA profile during the hepatic differentiation of hUC-MSCs provides the basis for clarifying the role of microRNAs in hUC-MSC hepatic differentiation and specific microRNA selection for the conversion of hUC-MSCs to hepatocytes.

Project description:BackgroundHuman umbilical cord mesenchymal stem cells (UC-MSCs) are multipotent progenitor cells representing an attractive therapeutic tool for tissue damage and inflammation owing to their unique immunomodulatory properties. This study was designed to determine the protective effects and underlying mechanisms of UC-MSCs on acute liver failure (ALF).MethodsALF was induced in mice by intraperitoneal injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS). Mice were intravenously injected with 1×106 UC-MSCs one hour before or six hours after D-GalN/LPS injection. Liver function was valued by serum biochemical parameters and hematoxylin-eosin staining. Inflammatory cytokine and chemokine levels were measured by real-time PCR, and inflammatory cells infiltration was observed by immunofluorescence staining. Hepatocyte apoptosis and pyroptosis related proteins were detected by western blot. Murine macrophage Raw264.7 in the presentation of LPS was treated with the UC-MSCs condition medium (UC-MSCs-CM), and then the levels of inflammatory cytokines and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in Raw264.7 were measured.ResultsUC-MSCs significantly reduced the mortality, decreased serum alanine aminotransferase and aspartate aminotransferase levels, and improved the pathological damage. Moreover, UC-MSCs inhibited inflammatory cytokine and chemokine levels, especially TNF-α, interleukins-6 (IL-6), IL-1β, monocyte chemoattractant protein (MCP-1), CC-chemokines ligand 2 (CCL2), C-X-C motif ligand 2 (CXCL2), and reduced macrophage, neutrophil and T lymphocyte infiltration into the liver tissue. UC-MSCs also attenuated hepatocyte apoptosis, as evidenced by decreased TUNEL positive cells, increased Bcl-xl/Bax protein ratio and downregulated cleaved caspase 3 levels. NLRP3 inflammasome activation, IL-1β maturation and cleaved caspase1 were suppressed by UC-MSC administration. Furthermore, the UC-MSCs-CM reduced the levels of inflammatory cytokines and the activation of NLRP3 inflammasome in Raw264.7.ConclusionsOur results demonstrated that UC-MSCs exerted therapeutic effects on ALF by inhibiting apoptosis, inflammation, and pyroptosis.

Dataset Information

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

Publications

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

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