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Advances in Mesenchymal stem cells regulating macrophage polarization and treatment of sepsis-induced liver injury

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Article Immunology

Mesenchymal stem cell-derived exosome alleviates sepsis- associated acute liver injury by suppressing MALAT1 through microRNA-26a-5p: an innovative immunopharmacological intervention and therapeutic approach for sepsis

Jizhen Cai et al.

Summary: This study investigated the roles and mechanisms of mesenchymal stem cells (MSCs) in the treatment of acute liver injury (ALI) induced by sepsis. The researchers found that MSCs or MSC-derived exosome significantly attenuated ALI and consequent death in sepsis. They also discovered that replenishment of miR-26a-5p protected against hepatocyte death and liver injury caused by sepsis through targeting MALAT1. These findings reveal the beneficial effects of MSCs, exosomes, and miR-26a-5p on ALI and provide insights into the potential mechanisms of ALI induced by sepsis.

FRONTIERS IN IMMUNOLOGY (2023)

Article Immunology

Mesenchymal Stem Cells Derived Extracellular Vesicles Alleviate Traumatic Hemorrhagic Shock Induced Hepatic Injury via IL-10/PTPN22-Mediated M2 Kupffer Cell Polarization

Yunwei Zhang et al.

Summary: In this study, it was discovered that mesenchymal stem cells (MSCs) can attenuate hepatic injury and inflammation caused by traumatic hemorrhagic shock (THS). Interleukin 10 (IL-10) plays a crucial role in this protective effect, and it is carried and delivered by MSC-derived extracellular vesicles (MSC-EVs). These EVs containing IL-10 mainly accumulate in the liver during THS, where they are captured by Kupffer cells and induce the expression of PTPN22, shifting Kupffer cells to an anti-inflammatory phenotype and mitigating liver inflammation and injury.

FRONTIERS IN IMMUNOLOGY (2022)

Review Pharmacology & Pharmacy

Mesenchymal Stem/Stromal Cells and Their Paracrine Activity-Immunomodulation Mechanisms and How to Influence the Therapeutic Potential

Rui Alvites et al.

Summary: Mesenchymal Stem/Stromal Cells (MSCs) have high clinical value and have been extensively studied. Their immunomodulatory influence occurs through both direct and paracrine routes, but the mechanisms are not fully understood. This review summarizes the immunoregulatory capacity of MSCs and their secretion products, with a focus on migration, homing, direct cell action, and paracrine activity, and explores related techniques.

PHARMACEUTICS (2022)

Article Gastroenterology & Hepatology

Transplantation of Mesenchymal Stem Cells Attenuates Acute Liver Failure in Mice via an Interleukin-4-dependent Switch to the M2 Macrophage Anti-inflammatory Phenotype

Jinglin Wang et al.

Summary: The study demonstrated that transplantation of MSCs can ameliorate acute liver failure (ALF) through an IL-4-dependent switch of macrophages to an anti-inflammatory phenotype, leading to hepatic regeneration. Overexpression of IL-4 may enhance the therapeutic effects of allogeneic MSC transplantation in the treatment of ALF.

JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY (2022)

Article Cell Biology

Use of integrated metabolomics, transcriptomics, and signal protein profile to characterize the effector function and associated metabotype of polarized macrophage phenotypes

Catherine B. Anders et al.

Summary: The study utilized an ex vivo model to generate 6 distinct functional phenotypes of macrophages, profiling them based on cell surface markers, secreted proteins, gene expression, and metabolites. The research identified unique metabolic profiles for each phenotype, grouping them into inflammatory and wound resolution categories, with key differences observed in metabolic pathways. Ultimately, the integration of metabolomics provided a comprehensive understanding of macrophage diversity and functional plasticity.

JOURNAL OF LEUKOCYTE BIOLOGY (2022)

Article Immunology

Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice

Wenchang Sun et al.

Summary: This study investigates the role of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) in systemic lupus erythematosus (SLE). The results show that hUC-MSC-derived exosomes have anti-inflammatory and immunomodulatory effects, alleviating organ injuries in SLE by inducing the polarization of M2 macrophages and regulatory T cells (Tregs). These exosomes may serve as a promising cell-free therapeutic strategy for SLE.

IMMUNOLOGICAL INVESTIGATIONS (2022)

Article Biochemistry & Molecular Biology

HNF4α overexpression enhances the therapeutic potential of umbilical cord mesenchymal stem/stromal cells in mice with acute liver failure

Yeping Yu et al.

Summary: Human umbilical cord mesenchymal stem/stromal cells (hUMSCs) overexpressing hepatocyte nuclear factor 4 alpha (HNF4 alpha) showed better therapeutic effects on acute liver failure (ALF) compared to hUMSCs without HNF4 alpha overexpression. The overexpression of HNF4 alpha enhanced IL-10 transcription and promoted M2 macrophage polarization through the IL-10/STAT3 pathway. This study suggests that HNF4 alpha-hUMSCs could serve as a novel therapy for ALF.

FEBS LETTERS (2022)

Article Multidisciplinary Sciences

Extracellular vesicles derived from GMSCs stimulated with TNF-α and IFN-α promote M2 macrophage polarization via enhanced CD73 and CD5L expression

Yukari Watanabe et al.

Summary: Priming gingival tissue-derived MSCs (GMSCs) with a combination of pro-inflammatory cytokines TNF-alpha and IFN-alpha can synergistically promote anti-inflammatory M2 macrophage polarization and increase the expression of CD73 and CD5L. This pre-licensing approach is significant in enhancing the anti-inflammatory function of EVs.

SCIENTIFIC REPORTS (2022)

Article Cell & Tissue Engineering

Notch-activated mesenchymal stromal/stem cells enhance the protective effect against acetaminophen-induced acute liver injury by activating AMPK/SIRT1 pathway

Mengxue Yu et al.

Summary: This study found that activation of Notch2 is necessary for MSCs to alleviate acute liver injury. Notch activation through the AMPK/SIRT1 signaling pathway reduces the activation of NLRP3 inflammasome, thus greatly enhancing the anti-inflammatory activity and therapeutic effects of MSCs.

STEM CELL RESEARCH & THERAPY (2022)

Article Cell & Tissue Engineering

Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages

Siyuan Tian et al.

Summary: This study found that mesenchymal stem cells (MSCs) protect against liver fibrosis by delivering miR-148a through their secreted exosomes (MSC-EXOs) to regulate intrahepatic macrophage functions. This finding provides a potential therapeutic target for liver fibrosis.

STEM CELL RESEARCH & THERAPY (2022)

Article Biochemistry & Molecular Biology

Hypoxic bone marrow mesenchymal stromal cells-derived exosomal miR-182-5p promotes liver regeneration via FOXO1-mediated macrophage polarization

Jing Xu et al.

Summary: Hypoxia preconditioning of mesenchymal stromal cells (Hp-MSCs) enhances liver regeneration through secreted exosomes (Hp-Exo), which mediate M2 macrophage polarization by modulating the FOXO1/TLR4 signaling pathway.

FASEB JOURNAL (2022)

Review Biochemistry & Molecular Biology

Pathophysiology of Sepsis and Genesis of Septic Shock: The Critical Role of Mesenchymal Stem Cells (MSCs)

Matthieu Daniel et al.

Summary: The treatment of sepsis and septic shock remains a major public health issue. Mesenchymal stem cells (MSCs) are emerging as a potential approach for cell therapy in sepsis, but the mechanisms underlying their beneficial effects are still unclear.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Cell Biology

Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis

Yuchen Pan et al.

Summary: Our study revealed that SPIO-labeled MSCs exert their therapeutic effects in sepsis mainly by enhancing the efferocytosis of macrophages and inducing ferroptosis of MSCs. MSCSPIO tended to stay longer in injured organs, playing a long-term protective role in sepsis.

CELL DEATH & DISEASE (2022)

Article Cell & Tissue Engineering

Human mesenchymal stromal cells small extracellular vesicles attenuate sepsis-induced acute lung injury in a mouse model: the role of oxidative stress and the mitogen-activated protein kinase/nuclear factor kappa B pathway

Jie Chen et al.

Summary: The study demonstrated the therapeutic effects of MSC-derived sEVs on sepsis-induced ALI in mice, showing improvements in lung injury, reduced inflammation, and increased antioxidant enzyme activity. Additionally, sEVs may exert their effects by inhibiting phosphorylation of the MAPK/NF-kappa B pathway and I kappa B degradation, while increasing the activity of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1.

CYTOTHERAPY (2021)

Article Cell & Tissue Engineering

Mesenchymal stem cell-secreted prostaglandin E2 ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization

Jinglin Wang et al.

Summary: Our results suggest that PGE(2) may be a novel important mediator of MSC in treating ALF, which inhibits liver inflammatory response and hepatocyte death by suppressing TAK1 signaling and NLRP3 inflammasome activation in liver macrophages, and promoting M2 macrophage polarization via STAT6 and mTOR signaling to limit liver injury.

STEM CELL RESEARCH & THERAPY (2021)

Article Cell & Tissue Engineering

microRNA-27b shuttled by mesenchymal stem cell-derived exosomes prevents sepsis by targeting JMJD3 and downregulating NF-κB signaling pathway

Jia Sun et al.

Summary: The study revealed that miR-27b highly expressed in exosomes derived from MSCs decreased the expression of pro-inflammatory genes by inhibiting the recruitment of JMJD3 and NF-kappa B, thereby reducing the production of pro-inflammatory cytokines in septic mice and LPS-treated BMDMs.

STEM CELL RESEARCH & THERAPY (2021)

Article Immunology

STAT6 up-regulation amplifies M2 macrophage anti-inflammatory capacity through mesenchymal stem cells

Yanwei Li et al.

Summary: In this study, it was found that mesenchymal stem cells induced M2 macrophage polarization by activating STAT6, leading to increased expression of anti-inflammatory factors to alleviate acute liver failure.

INTERNATIONAL IMMUNOPHARMACOLOGY (2021)

Article Cell & Tissue Engineering

SPION-MSCs enhance therapeutic efficacy in sepsis by regulating MSC-expressed TRAF1-dependent macrophage polarization

Yujun Xu et al.

Summary: The study demonstrated that SPIONs did not affect the basic characteristics of MSCs and even promoted their survival in inflammatory conditions. SPION-MSCs enhanced the therapeutic efficacy of liver injury in sepsis animal models, with this protective effect being related to macrophages.

STEM CELL RESEARCH & THERAPY (2021)

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Sepsis

Michael H. Ackerman et al.

CRITICAL CARE NURSING CLINICS OF NORTH AMERICA (2021)

Review Immunology

Anti-inflammatory and M2 macrophage polarization-promoting effect of mesenchymal stem cell-derived exosomes

Maedeh Arabpour et al.

Summary: MSC-derived exosomes have the potential to polarize M2 macrophages and modulate inflammation in various diseases and conditions like CNS diseases, autoimmune diseases, inflammatory bowel disease, and cardiomyopathy.

INTERNATIONAL IMMUNOPHARMACOLOGY (2021)

Article Cell & Tissue Engineering

Human umbilical cord-derived mesenchymal stem cells improve the function of liver in rats with acute-on-chronic liver failure via downregulating Notch and Stat1/Stat3 signaling

Yulin He et al.

Summary: The transplantation of hUC-MSCs can improve liver function, degree of fibrosis, and liver damage in rats with ACLI or ACLF, likely mediated by inhibiting Notch signaling and reversing the imbalance of the Stat1/Stat3 pathway.

STEM CELL RESEARCH & THERAPY (2021)

Article Cell & Tissue Engineering

Placental chorionic plate-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating macrophage polarization via secreting TSG-6

Qilin Huang et al.

Summary: The study demonstrated that placental chorionic plate-derived MSCs can survive in injured tissues of SAP rats, reducing pancreatic injury and systemic inflammation by inducing macrophages to polarize from M1 to M2. The mechanism involves the secretion of TSG-6 by CP-MSCs, which plays a vital role in mitigating pancreatic injury and systemic inflammation in SAP rats.

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Janus kinases (JAKs): The efficient therapeutic targets for autoimmune diseases and myeloproliferative disorders

Pengfei Xu et al.

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Mesenchymal stem cells: Cell therapy and regeneration potential

Christina Brown et al.

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Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages

Linrui Jiang et al.

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The Roles of Notch Signaling in Liver Development and Disease

Joshua M. Adams et al.

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Mechanisms and treatment of organ failure in sepsis

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Pavel Strnad et al.

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Liver macrophages in tissue homeostasis and disease

Oliver Krenkel et al.

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Bin Cai et al.

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Ruenn Chai Lai et al.

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Jun Yan et al.

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Effect of siRNA against NF-κB on sepsis-induced acute lung injury in a mouse model

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David F. Gaieski et al.

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Kupffer Cells in the Liver

Laura J. Dixon et al.

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Macrophage plasticity and polarization: in vivo veritas

Antonio Sica et al.

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Population Burden of Long-Term Survivorship After Severe Sepsis in Older Americans

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HEPATIC FIBROSIS IN A LONG-TERM MURINE MODEL OF SEPSIS

Falk A. Gonnert et al.

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Living in the liver: hepatic infections

Ulrike Protzer et al.

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Mesenchymal Stem Cell Homing: The Devil Is in the Details

Jeffrey M. Karp et al.

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Severe Sepsis in Cirrhosis

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Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor κB

Chiara Porta et al.

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Patients with acute on chronic liver failure display 'sepsis-like' immune paralysis

HE Wasmuth et al.

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JF Dhainaut et al.

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