MiR-200b in heme oxygenase-1-modified bone marrow mesenchymal stem cell-derived exosomes alleviates inflammatory injury of intestinal epithelial cells by targeting high mobility group box 3

Sun, Dong; Cao, Huấn; Liu, Yang; Li, Gang; Hou, Bin; Zheng, Weiping; Shen, Zhongyang; Song, Hongli

doi:10.1038/s41419-020-2685-8

Cited by 36 publications

(27 citation statements)

References 72 publications

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“…Isolation and Identification of HO-1/BMMSCs. The isolation, culture, identification, and gene transfection of BMMSCs were carried out as described previously [9,10]. Bone marrow contents were extracted from the rat femur and tibia, and BMMSCs were obtained by the continuous adhesion method [13].…”

Section: 3mentioning

confidence: 99%

“…However, the ability of MSCs to “home” to injured tissue is controversial, because most MSCs are actually trapped in pulmonary capillaries after intravenous administration [ 5 ]. Previous studies have shown that normothermic machine perfusion (NMP) could promote engraftment of bone marrow mesenchymal stem cells (BMMSCs) in the liver, and heme oxygenase-1 (HO-1) could prolong the survival of BMMSCs in the injured site [ 9 , 10 ]. Therefore, in the present study, we aimed to infuse HO-1-modified BMMSCs (HO-1/BMMSCs) into the liver using NMP.…”

Section: Introductionmentioning

confidence: 99%

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Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway

Tian

Cao

et al. 2021

Stem Cells International

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Livers from donors after circulatory death (DCD) are inevitably exposed to a longer warm ischemic period, which might increase the incidence of postoperative bile duct complications. Bone marrow mesenchymal stem cells (BMMSCs) have tissue repair properties. The present study was aimed at exploring the repair effect of heme oxygenase-1- (HO-1-) modified BMMSCs (HO-1/BMMSCs) combined with normothermic machine perfusion (NMP) on bile duct injury after DCD liver transplantation and at revealing the underlying mechanisms. Rat livers were exposed to in situ warm ischemia for 30 min; then, NMP was performed through the portal vein for 4 h with BMMSCs, HO-1/BMMSCs, or neither before implantation. Obvious bile duct histological damage and liver functional damage were observed postoperatively. In the group treated with HO-1/BMMSCs combined with NMP (HBP group), liver functions and bile duct histology were improved; meanwhile, cell apoptosis was reduced and cell proliferation was active. A large number of regenerative cells appeared at the injured site, and the defective bile duct epithelium was restored. Dilatation of peribiliary glands (PBGs), proliferation of PBG cells, high expression of vascular endothelial growth factor (VEGF), and increased proportion of bile duct progenitor cells with stem/progenitor cells biomarkers were observed. Blocking Wnt signaling significantly inhibited the repair effect of HO-1/BMMSCs on bile duct injury. In conclusion, HO-1/BMMSCs combined with NMP were relevant to the activation of biliary progenitor cells in PBGs which repaired bile duct injury in DCD liver transplantation via the Wnt signaling pathway. Proliferation and differentiation of PBG cells were involved in the renewal of the injured biliary epithelium.

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Section: 3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway

Tian

Cao

et al. 2021

Stem Cells International

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“…Regarding the potential beneficial effect of the miRNA content in EVs in this pathology, a crucial role of exosomal miR200b has been described by using heme oxygenase-1 (HO-1)-modified bone marrow MSC-Exo, which overexpresses miR200b. This miRNA targets the HMGB3 gene involved in intestinal inflammation (284). Moreover, EVs overexpressing miR-146a seem to exert better anti-inflammatory effects in an experimental rat model of colitis (285).…”

Section: Msc-evs and Intestinal Injurymentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

et al. 2021

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Severe trauma is the principal cause of death among young people worldwide. Hemorrhagic shock is the leading cause of death after severe trauma. Traumatic hemorrhagic shock (THS) is a complex phenomenon associating an absolute hypovolemia secondary to a sudden and significant extravascular blood loss, tissue injury, and, eventually, hypoxemia. These phenomena are responsible of secondary injuries such as coagulopathy, endotheliopathy, microcirculation failure, inflammation, and immune activation. Collectively, these dysfunctions lead to secondary organ failures and multi-organ failure (MOF). The development of MOF after severe trauma is one of the leading causes of morbidity and mortality, where immunological dysfunction plays a central role. Damage-associated molecular patterns induce an early and exaggerated activation of innate immunity and a suppression of adaptive immunity. Severe complications are associated with a prolonged and dysregulated immune–inflammatory state. The current challenge in the management of THS patients is preventing organ injury, which currently has no etiological treatment available. Modulating the immune response is a potential therapeutic strategy for preventing the complications of THS. Mesenchymal stromal cells (MSCs) are multipotent cells found in a large number of adult tissues and used in clinical practice as therapeutic agents for immunomodulation and tissue repair. There is growing evidence that their efficiency is mainly attributed to the secretion of a wide range of bioactive molecules and extracellular vesicles (EVs). Indeed, different experimental studies revealed that MSC-derived EVs (MSC-EVs) could modulate local and systemic deleterious immune response. Therefore, these new cell-free therapeutic products, easily stored and available immediately, represent a tremendous opportunity in the emergency context of shock. In this review, the pathophysiological environment of THS and, in particular, the crosstalk between the immune system and organ function are described. The potential therapeutic benefits of MSCs or their EVs in treating THS are discussed based on the current knowledge. Understanding the key mechanisms of immune deregulation leading to organ damage is a crucial element in order to optimize the preparation of EVs and potentiate their therapeutic effect.

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“…HMGB3 is a DNA-binding protein that helps maintain stem cell populations and is overexpressed in some human cancers via the Wnt signaling pathway [ 74 , 75 ]. Further, HMGB3 affects nucleic acid recognition and innate immune system activation, and its upregulation has been associated with allograft rejection [ 76 – 79 ]. Therefore, higher baseline expression of HMGB3 in female devils may enhance the innate immune response to DFTD relative to males.…”

Section: Discussionmentioning

confidence: 99%

Spatial variation in gene expression of Tasmanian devil facial tumors despite minimal host transcriptomic response to infection

et al. 2021

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Background Transmissible cancers lie at the intersection of oncology and infectious disease, two traditionally divergent fields for which gene expression studies are particularly useful for identifying the molecular basis of phenotypic variation. In oncology, transcriptomics studies, which characterize the expression of thousands of genes, have identified processes leading to heterogeneity in cancer phenotypes and individual prognoses. More generally, transcriptomics studies of infectious diseases characterize interactions between host, pathogen, and environment to better predict population-level outcomes. Tasmanian devils have been impacted dramatically by a transmissible cancer (devil facial tumor disease; DFTD) that has led to widespread population declines. Despite initial predictions of extinction, populations have persisted at low levels, due in part to heterogeneity in host responses, particularly between sexes. However, the processes underlying this variation remain unknown. Results We sequenced transcriptomes from healthy and DFTD-infected devils, as well as DFTD tumors, to characterize host responses to DFTD infection, identify differing host-tumor molecular interactions between sexes, and investigate the extent to which tumor gene expression varies among host populations. We found minimal variation in gene expression of devil lip tissues, either with respect to DFTD infection status or sex. However, 4088 genes were differentially expressed in tumors among our sampling localities. Pathways that were up- or downregulated in DFTD tumors relative to normal tissues exhibited the same patterns of expression with greater intensity in tumors from localities that experienced DFTD for longer. No mRNA sequence variants were associated with expression variation. Conclusions Expression variation among localities may reflect morphological differences in tumors that alter ratios of normal-to-tumor cells within biopsies. Phenotypic variation in tumors may arise from environmental variation or differences in host immune response that were undetectable in lip biopsies, potentially reflecting variation in host-tumor coevolutionary relationships among sites that differ in the time since DFTD arrival.

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MiR-200b in heme oxygenase-1-modified bone marrow mesenchymal stem cell-derived exosomes alleviates inflammatory injury of intestinal epithelial cells by targeting high mobility group box 3

Cited by 36 publications

References 72 publications

Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway

Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway

Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock

Spatial variation in gene expression of Tasmanian devil facial tumors despite minimal host transcriptomic response to infection

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