A novel therapeutic approach for inflammatory bowel disease by exosomes derived from human umbilical cord mesenchymal stem cells to repair intestinal barrier via TSG-6

Yang, Shaopeng; Liang, Xueya; Song, Jia; Li, Chenyang; Liu, Airu; Luo, Yuxin; Ma, Huimin; Tan, Yi; Zhang, Xiaolan

doi:10.1186/s13287-021-02404-8

Cited by 106 publications

(103 citation statements)

References 50 publications

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“…We were able to successfully isolate and culture UC-MSCs from the fresh umbilical cord ( Zheng et al, 2020 ; Yang et al, 2021 ). The UC-MSCs displayed as spindle-shaped cells crawled out of the tissue pieces when the tissue blocks adhered to the bottom of the culture flask within the medium for 7–10 days ( Figure 2A ).…”

Section: Resultsmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cells Improve Locomotor Function in Parkinson’s Disease Mouse Model Through Regulating Intestinal Microorganisms

Sun

et al. 2022

Front. Cell Dev. Biol.

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Parkinson’s disease (PD) is a progressive neurological disorder characterized by loss of neurons that synthesize dopamine, and subsequent impaired movement. Umbilical cord mesenchymal stem cells (UC-MSCs) exerted neuroprotection effects in a rodent model of PD. However, the mechanism underlying UC-MSC-generated neuroprotection was not fully elucidated. In the present study, we found that intranasal administration of UC-MSCs significantly alleviated locomotor deficits and rescued dopaminergic neurons by inhibiting neuroinflammation in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, a toxic agent which selectively destroys nigrostriatal neurons but does not affect dopaminergic neurons elsewhere). Furthermore, UC-MSC treatment altered gut microbiota composition characterized by decreased phylum Proteobacteria, class Gammaproteobacteria, family Enterobacteriaceae, and genus Escherichia-Shigella. In addition, the neurotransmitter dopamine in the striatum and 5-hydroxytryptamine in the colon were also modulated by UC-MSCs. Meanwhile, UC-MSCs significantly maintained intestinal goblet cells, which secrete mucus as a mechanical barrier against pathogens. Furthermore, UC-MSCs alleviate the level of TNF-α and IL-6 as well as the conversion of NF-κB expression in the colon, indicating that inflammatory responses were blocked by UC-MSCs. PICRUSt showed that some pathways including bacterial invasion of epithelial cells, fluorobenzoate degradation, and pathogenic Escherichia coli infection were significantly reversed by UC-MSCs. These data suggest that the beneficial effects were detected following UC-MSC intranasal transplantation in MPTP-treated mice. There is a possible neuroprotective role of UC-MSCs in MPTP-induced PD mice by cross talk between the brain and gut.

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Section: Resultsmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cells Improve Locomotor Function in Parkinson’s Disease Mouse Model Through Regulating Intestinal Microorganisms

Sun

et al. 2022

Front. Cell Dev. Biol.

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“…Moreover, intraperitoneal injection of MSC-Exo in a mouse model of inflammatory bowel disease indicated a protective role in the intestinal barrier not only by preventing the destruction of tight junctions, therefore decreasing permeability, but also by modulating the responses of Th2 and Th17 cells in the mesenteric lymph nodes. Again, the knockdown of TSG-6 abrogated the therapeutic effects of MSC-Exo; conversely, administration of a recombinant of TSG-6 showed beneficial effects similar to those of MSC-Exo ( 286 ). Therefore, TSG-6 appears to play a major role in the anti-inflammatory effects of MSC-EVs in inflammatory bowel pathologies.…”

Section: Immuno-properties Of Msc-evs and Mofmentioning

confidence: 94%

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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“…IBD, which primarily includes ulcerative colitis (UC) and Crohn’s disease (CD), has become a global disease with an increasing incidence ( 118 ). Studies of this disease have mainly used DSS and 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce IBD in mouse models ( 119 ). Existing drugs to treat IBD are still very limited, Therefore, there is an urgent need to develop safe and effective treatments for IBD ( 120 ).…”

Section: Applications Of Mesenchymal Stem Cell-derived Exosomes In Autoimmune Diseasesmentioning

confidence: 99%

“…hUC-MSC-EXOs also inhibited neddylation and alleviated IBD by miR-326 ( 122 ). Another study also showed that exosomal miRNA of MSCs, such us miR-146a, downregulated TNF receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK1) expression, inhibited pro-inflammatory cytokine and enhanced the expression of IL-10 ( 123 ).Moreover, tumor necrosis factor-α stimulated gene 6 (TSG-6), as detected by hUC-MSC-EXOs, regulated the immune response of Th2 and Th17 cells in mesenteric lymph nodes (MLN), down-regulated the levels of pro-inflammatory cytokines in colon tissue, and up-regulated the levels of anti-inflammatory cytokines to protect the intestinal barrier ( 119 ). Other tissue-derived MSC-EXOs showed similar efficacy to that of hUC-MSC-EXOs in the treatment of DSS induced IBD.…”

Section: Applications Of Mesenchymal Stem Cell-derived Exosomes In Autoimmune Diseasesmentioning

confidence: 99%

Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases

et al. 2021

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Recent years, the immunosuppressive properties of mesenchymal stem cells (MSCs) have been demonstrated in preclinical studies and trials of inflammatory and autoimmune diseases. Emerging evidence indicates that the immunomodulatory effect of MSCs is primarily attributed to the paracrine pathway. As one of the key paracrine effectors, mesenchymal stem cell-derived exosomes (MSC-EXOs) are small vesicles 30-200 nm in diameter that play an important role in cell-to-cell communication by carrying bioactive substances from parental cells. Recent studies support the finding that MSC-EXOs have an obvious inhibitory effect toward different effector cells involved in the innate and adaptive immune response. Moreover, substantial progress has been made in the treatment of autoimmune diseases, including multiple sclerosis (MS), systemic lupus erythematosus (SLE), type-1 diabetes (T1DM), uveitis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSC-EXOs are capable of reproducing MSC function and overcoming the limitations of traditional cell therapy. Therefore, using MSC-EXOs instead of MSCs to treat autoimmune diseases appears to be a promising cell-free treatment strategy. In this review, we review the current understanding of MSC-EXOs and discuss the regulatory role of MSC-EXOs on immune cells and its potential application in autoimmune diseases.

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A novel therapeutic approach for inflammatory bowel disease by exosomes derived from human umbilical cord mesenchymal stem cells to repair intestinal barrier via TSG-6

Cited by 106 publications

References 50 publications

Human Umbilical Cord Mesenchymal Stem Cells Improve Locomotor Function in Parkinson’s Disease Mouse Model Through Regulating Intestinal Microorganisms

Human Umbilical Cord Mesenchymal Stem Cells Improve Locomotor Function in Parkinson’s Disease Mouse Model Through Regulating Intestinal Microorganisms

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

Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases

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