Exosomes derived from hypoxic bone marrow mesenchymal stem cells rescue OGD-induced injury in neural cells by suppressing NLRP3 inflammasome-mediated pyroptosis

Kang, Xiuwen; Jiang, Lei; Chen, Xufeng; Wang, Xi; Gu, Shuangshuang; Wang, Jun; Zhu, Yuanhui; Xiao, Hang; Zhang, Jinsong

doi:10.1016/j.yexcr.2021.112635

Cited by 28 publications

(16 citation statements)

References 28 publications

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“…The expression of NLRP3, ASC, Caspase-1, GSDMD-N, cleaved IL-1β and IL-18 were decreased in neuron cells after taking up bone marrow mesenchymal stromal cells-derived exosomes. Hypoxic exosomes had more significant effects to decrease these molecules, and exhibited a more pronounced neuroprotective effect against oxygen-glucose deprivation injury ( 159 ). MiR-21 was also reported to be increased by hypoxia in exosomes derived from mesenchymal stromal cells and mediated the improvement of neurologic conditions.…”

Section: Hypoxic Exosomes In Non-malignant Disease From Different Sys...mentioning

confidence: 99%

Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects

et al. 2022

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Exosomes are small extracellular vesicles that are secreted by almost all types of cells and exist in almost all extracellular spaces. As an important mediator of intercellular communication, exosomes encapsulate the miRNA, lncRNA, cirRNA, mRNA, cytokine, enzyme, lipid, and other components from the cytoplasm into its closed single membrane structure and transfer them to recipient units in an autocrine, paracrine, or endocrine manner. Hypoxia is a state of low oxygen tension and is involved in many pathological processes. Hypoxia influences the size, quantity, and expression of exosome cargos. Exosomes derived from hypoxic tumor cells transfer genetics, proteins, and lipids to the recipient units to exert pleiotropic effects. Different donor cells produce different cargo contents, target different recipient units and lead to different biological effects. Hypoxic exosomes derived from tumor cells uptaken by normoxic tumor cells lead to promoted proliferation, migration, and invasion; uptaken by extracellular space or liver lead to promoted metastasis; uptaken by endothelial cells lead to promoted angiogenesis; uptaken by immune cells lead to promoted macrophage polarization and changed tumor immune microenvironment. In addition to various types of tumors, hypoxic exosomes also participate in the development of diseases in the cardiovascular system, neuron system, respiratory system, hematology system, endocrine system, urinary system, reproduction system, and skeletomuscular system. Understanding the special characteristics of hypoxic exosomes provide new insight into elaborating the pathogenesis of hypoxia related disease. This review summarizes hypoxia induced cargo changes and the biological effects of hypoxic exosomes in tumors and non-malignant diseases in different systems.

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Section: Hypoxic Exosomes In Non-malignant Disease From Different Sys...mentioning

confidence: 99%

Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects

et al. 2022

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“…Hypoxia preconditioned MSCs generally possessed increased paracrine effect, better cell survival rate, augmented homing abilities, and integration to injury sites 32–34 . Recent evidence suggests that hypoxia pre‐challenged MSCs exhibit enhanced angiogenesis and tissue regeneration 35 . However, it is still unclear whether MSCs exposed to hypoxic conditions exhibit better therapeutic efficacy to enhance liver regeneration, and whether such an advantage is mediated by the secreted Exo.…”

Section: Introductionmentioning

confidence: 99%

“…[32][33][34] Recent evidence suggests that hypoxia pre-challenged MSCs exhibit enhanced angiogenesis and tissue regeneration. 35 However, it is still unclear whether MSCs exposed to hypoxic conditions exhibit better therapeutic efficacy to enhance liver regeneration, and whether such an advantage is mediated by the secreted Exo.…”

Section: Introductionmentioning

confidence: 99%

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

Chen

et al. 2022

The FASEB Journal

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Mesenchymal stromal cells (MSCs) are attractive candidates for treating hepatic disorders given their potential to enhance liver regeneration and function. The paracrine paradigm may be involved in the mechanism of MSC-based therapy, and exosomes (Exo) play an important role in this paracrine activity. Hypoxia significantly improves the effectiveness of MSC transplantation. However, whether hypoxia preconditioned MSCs (Hp-MSCs) can enhance liver regeneration, and whether this enhancement is mediated by Exo, are unknown. In this study, mouse bone marrow-derived MSCs (BM-MSCs) and secreted Exo were injected through the tail vein. We report that Hp-MSCs promote liver regeneration after partial hepatectomy in mice through their secreted exosomes. Interestingly, MSC-Exo were concentrated in liver 6 h after administration and mainly taken up by macrophages, but not hepatocytes. Compared with normoxic MSC-Exo (N-Exo), hypoxic MSC-Exo (Hp-Exo) enhanced M2 macrophage polarization both in vivo and in vitro. Microarray analysis revealed significant enrichment of microRNA (miR)-182-5p in Hp-Exo compared with that in N-Exo. In addition, miR-182-5p knockdown partially abolished the beneficial effect of Hp-Exo. Finally, Hp-MSCderived exosomal miR-182-5p inhibited theprotein expression of forkhead box transcription factor 1 (FOXO1) in macrophages, which inhibited toll-like receptor Research), Grant/Award Number: 2018YFA0109800; China Postdoctoral Science Foundation, Grant/Award Number: 2019M652328 4 (TLR4) expression and subsequently induced an anti-inflammatory response. These results highlight the therapeutic potential of Hp-Exo in liver regeneration and suggest that miR-182-5p from Hp-Exo facilitates macrophage polarization during liver regeneration by modulating the FOXO1/TLR4 signaling pathway.

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“…The cardiac benefits of MSCs come through their paracrine of EVs, soluble proteins, etc [ 26 , 27 ]. Exosomal secretion involves various environmental factors [ 28 ]. Under hypoxia, more exosomes are secreted, and HIF-1α may mediate this process [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction

Wang

Zhang

Sun

et al. 2021

Materials Today Bio

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Aims Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1α engineered mesenchymal stem cells (MSCs) in a rat model of AMI. Methods and results EVs isolated from HIF-1α engineered MSCs (HIF-1α-EVs) and control MSCs (NC-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with NC-EVs, HIF-1α-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1α-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1α-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221–3p was highly expressed in HIF-1α-EVs. After miR-221–3p was inhibited in HIF-1α-EVs, the biological effects of HIF-1α EVs on apoptosis and angiogenesis were attenuated. Conclusion EVs released by MSCs with HIF-1α overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221–3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1α engineered MSCs-derived EVs.

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Exosomes derived from hypoxic bone marrow mesenchymal stem cells rescue OGD-induced injury in neural cells by suppressing NLRP3 inflammasome-mediated pyroptosis

Cited by 28 publications

References 28 publications

Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects

Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects

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

HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction

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