Bibliographies thématiques / Mesenchymal stromal cells, extracellular vesicles, immunoregulatory properties and inflammation

Littérature scientifique sur le sujet « Mesenchymal stromal cells, extracellular vesicles, immunoregulatory properties and inflammation »

Auteur : Grafiati

Publié le 11 mars 2023

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Articles de revues sur le sujet "Mesenchymal stromal cells, extracellular vesicles, immunoregulatory properties and inflammation"

Gorgun, Cansu, Chiara Africano, Maria Chiara Ciferri, Nadia Bertola, Daniele Reverberi, Rodolfo Quarto, Silvia Ravera et Roberta Tasso. « Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles (EVs) Counteract Inflammaging ». Cells 11, n^o 22 (21 novembre 2022) : 3695. http://dx.doi.org/10.3390/cells11223695.

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Inflammaging is one of the evolutionarily conserved mechanisms underlying aging and is defined as the long-term consequence of the chronic stimulation of the innate immune system. As macrophages are intimately involved in initiating and regulating the inflammatory process, their dysregulation plays major roles in inflammaging. The paracrine factors, and in particular extracellular vesicles (EVs), released by mesenchymal stromal cells (MSCs) retain immunoregulatory effects on innate and adaptive immune responses. In this paper, we demonstrate that EVs derived from MSCs preconditioned with hypoxia inflammatory cytokines exerted an anti-inflammatory role in the context of inflammaging. In this study, macrophages isolated from aged mice presented elevated pro-inflammatory factor levels already in basal conditions compared to the young counterpart, and this pre-activation status increased when cells were challenged with IFN-γ. EVs were able to attenuate the age-associated inflammation, inducing a decrease in the expression of TNF-α, iNOS, and the NADase CD38. Moreover, we demonstrate that EVs counteracted the mitochondrial dysfunction that affected the macrophages, reducing lipid peroxidation and hindering the age-associated impairment of mitochondrial complex I activity, oxygen consumption, and ATP synthesis. These results indicate that preconditioned MSC-derived EVs might be exploited as new anti-aging therapies in a variety of age-related diseases.

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Matheakakis, Angelos, Aristea Batsali, Helen A. Papadaki et Charalampos G. Pontikoglou. « Therapeutic Implications of Mesenchymal Stromal Cells and Their Extracellular Vesicles in Autoimmune Diseases : From Biology to Clinical Applications ». International Journal of Molecular Sciences 22, n^o 18 (20 septembre 2021) : 10132. http://dx.doi.org/10.3390/ijms221810132.

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Mesenchymal stromal cells (MSCs) are perivascular multipotent stem cells originally identified in the bone marrow (BM) stroma and subsequently in virtually all vascularized tissues. Because of their ability to differentiate into various mesodermal lineages, their trophic properties, homing capacity, and immunomodulatory functions, MSCs have emerged as attractive candidates in tissue repair and treatment of autoimmune disorders. Accumulating evidence suggests that the beneficial effects of MSCs may be primarily mediated via a number of paracrine-acting soluble factors and extracellular vesicles (EVs). EVs are membrane-coated vesicles that are increasingly being acknowledged as playing a key role in intercellular communication via their capacity to carry and deliver their cargo, consisting of proteins, nucleic acids, and lipids to recipient cells. MSC-EVs recapitulate the functions of the cells they originate, including immunoregulatory effects but do not seem to be associated with the limitations and concerns of cell-based therapies, thereby emerging as an appealing alternative therapeutic option in immune-mediated disorders. In the present review, the biology of MSCs will be outlined and an overview of their immunomodulatory functions will be provided. In addition, current knowledge on the features of MSC-EVs and their immunoregulatory potential will be summarized. Finally, therapeutic applications of MSCs and MSC-EVs in autoimmune disorders will be discussed.

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Harrell, Carl Randall, Vladislav Volarevic, Valentin Djonov et Ana Volarevic. « Therapeutic Potential of Exosomes Derived from Adipose Tissue-Sourced Mesenchymal Stem Cells in the Treatment of Neural and Retinal Diseases ». International Journal of Molecular Sciences 23, n^o 9 (19 avril 2022) : 4487. http://dx.doi.org/10.3390/ijms23094487.

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Therapeutic agents that are able to prevent or attenuate inflammation and ischemia-induced injury of neural and retinal cells could be used for the treatment of neural and retinal diseases. Exosomes derived from adipose tissue-sourced mesenchymal stem cells (AT-MSC-Exos) are extracellular vesicles that contain neurotrophins, immunoregulatory and angio-modulatory factors secreted by their parental cells. AT-MSC-Exos are enriched with bioactive molecules (microRNAs (miRNAs), enzymes, cytokines, chemokines, immunoregulatory, trophic, and growth factors), that alleviate inflammation and promote the survival of injured cells in neural and retinal tissues. Due to the nano-sized dimension and bilayer lipid envelope, AT-MSC-Exos easily bypass blood–brain and blood–retinal barriers and deliver their cargo directly into the target cells. Accordingly, a large number of experimental studies demonstrated the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases. By delivering neurotrophins, AT-MSC-Exos prevent apoptosis of injured neurons and retinal cells and promote neuritogenesis. AT-MSC-Exos alleviate inflammation in the injured brain, spinal cord, and retinas by delivering immunoregulatory factors in immune cells, suppressing their inflammatory properties. AT-MSC-Exos may act as biological mediators that deliver pro-angiogenic miRNAs in endothelial cells, enabling re-vascularization of ischemic neural and retinal tissues. Herewith, we summarized current knowledge about molecular mechanisms which were responsible for the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases, emphasizing their therapeutic potential in neurology and ophthalmology.

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Alberti, Giusi, Eleonora Russo, Simona Corrao, Rita Anzalone, Peter Kruzliak, Vitale Miceli, Pier Giulio Conaldi, Francesca Di Gaudio et Giampiero La Rocca. « Current Perspectives on Adult Mesenchymal Stromal Cell-Derived Extracellular Vesicles : Biological Features and Clinical Indications ». Biomedicines 10, n^o 11 (5 novembre 2022) : 2822. http://dx.doi.org/10.3390/biomedicines10112822.

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Extracellular vesicles (EVs) constitute one of the main mechanisms by which cells communicate with the surrounding tissue or at distance. Vesicle secretion is featured by most cell types, and adult mesenchymal stromal cells (MSCs) of different tissue origins have shown the ability to produce them. In recent years, several reports disclosed the molecular composition and suggested clinical indications for EVs derived from adult MSCs. The parental cells were already known for their roles in different disease settings in regulating inflammation, immune modulation, or transdifferentiation to promote cell repopulation. Interestingly, most reports also suggested that part of the properties of parental cells were maintained by isolated EV populations. This review analyzes the recent development in the field of cell-free therapies, focusing on several adult tissues as a source of MSC-derived EVs and the available clinical data from in vivo models.

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Ragni, Enrico, Carlotta Perucca Orfei et Laura de Girolamo. « Secreted Factors and Extracellular Vesicles Account for the Immunomodulatory and Tissue Regenerative Properties of Bone-Marrow-Derived Mesenchymal Stromal Cells for Osteoarthritis ». Cells 11, n^o 21 (4 novembre 2022) : 3501. http://dx.doi.org/10.3390/cells11213501.

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Bone-marrow-derived mesenchymal stromal cells (BMSCs) showed therapeutic potential in the treatment of musculoskeletal diseases, including osteoarthritis (OA). Their soluble mediators and extracellular vesicles (EVs), which make up the secretome, suppress immune response, attenuate inflammation and promote cartilage repair. EVs, as well as the whole secretome, have been investigated as cell free approaches for OA although, to date, a disease-tailored molecular fingerprint is missing. In this study, soluble mediators and miRNAs were sifted in the BMSCs’ secretome and EVs, respectively, and analyzed in the frame of cell types and factors involved in OA. The majority of identified molecules repress the activation of immune cells and the production of OA-related inflammatory mediators, as well as promote cartilage protection by acting on both chondrocytes homeostasis and extracellular matrix-degrading enzymes. These data provide the molecular ground for the therapeutic potential of BMSCs for regenerative applications for OA and support the use of secretome or EVs as cell-free applications in joint diseases.

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Massa, Margherita, Stefania Croce, Rita Campanelli, Carlotta Abbà, Elisa Lenta, Chiara Valsecchi et Maria Antonietta Avanzini. « Clinical Applications of Mesenchymal Stem/Stromal Cell Derived Extracellular Vesicles : Therapeutic Potential of an Acellular Product ». Diagnostics 10, n^o 12 (24 novembre 2020) : 999. http://dx.doi.org/10.3390/diagnostics10120999.

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In the last decade, the secreting activity of mesenchymal stem/stromal cells (MSCs) has been widely investigated, due to its possible therapeutic role. In fact, MSCs release extracellular vesicles (EVs) containing relevant biomolecules such as mRNAs, microRNAs, bioactive lipids, and signaling receptors, able to restore physiological conditions where regenerative or anti-inflammatory actions are needed. An actual advantage would come from the therapeutic use of EVs with respect to MSCs, avoiding the possible immune rejection, the lung entrapment, improving the safety, and allowing the crossing of biological barriers. A number of concerns still have to be solved regarding the mechanisms determining the beneficial effect of MSC-EVs, the possible alteration of their properties as a consequence of the isolation/purification methods, and/or the best approach for a large-scale production for clinical use. Most of the preclinical studies have been successful, reporting for MSC-EVs a protecting role in acute kidney injury following ischemia reperfusion, a potent anti-inflammatory and anti-fibrotic effects by reducing disease associated inflammation and fibrosis in lung and liver, and the modulation of both innate and adaptive immune responses in graft versus host disease (GVHD) as well as autoimmune diseases. However, the translation of MSC-EVs to the clinical stage is still at the initial phase. Herein, we discuss the therapeutic potential of an acellular product such as MSC derived EVs (MSC-EVs) in acute and chronic pathologies.

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Clark, Kaitlin, Sheng Zhang, Sylvain Barthe, Priyadarsini Kumar, Christopher Pivetti, Nicole Kreutzberg, Camille Reed et al. « Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration in an Animal Model of Multiple Sclerosis ». Cells 8, n^o 12 (23 novembre 2019) : 1497. http://dx.doi.org/10.3390/cells8121497.

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Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss. In the current study, an induced experimental autoimmune encephalomyelitis (EAE) murine model of MS was utilized. At peak disease onset, animals were treated with saline, placenta-derived MSCs (PMSCs), as well as low and high doses of PMSC-EVs. Animals treated with PMSCs and high-dose PMSC-EVs displayed improved motor function outcomes as compared to animals treated with saline. Symptom improvement by PMSCs and PMSC-EVs led to reduced DNA damage in oligodendroglia populations and increased myelination within the spinal cord of treated mice. In vitro data demonstrate that PMSC-EVs promote myelin regeneration by inducing endogenous oligodendrocyte precursor cells to differentiate into mature myelinating oligodendrocytes. These findings support that PMSCs’ mechanism of action is mediated by the secretion of EVs. Therefore, PMSC-derived EVs are a feasible alternative to cellular based therapies for MS, as demonstrated in an animal model of the disease.

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Pers, Yves-Marie, Claire Bony, Isabelle Duroux-Richard, Laurène Bernard, Marie Maumus, Said Assou, Frank Barry, Christian Jorgensen et Danièle Noël. « miR-155 Contributes to the Immunoregulatory Function of Human Mesenchymal Stem Cells ». Frontiers in Immunology 12 (26 mars 2021). http://dx.doi.org/10.3389/fimmu.2021.624024.

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ObjectivesMesenchymal stem/stromal cells (MSCs) are widely investigated in regenerative medicine thanks to their immunomodulatory properties. They exert their anti-inflammatory function thanks to the secretion of a number of mediators, including proteins and miRNAs, which can be released in the extracellular environment or in the cargo of extracellular vesicles (EVs). However, the role of miRNAs in the suppressive function of MSCs is controversial. The aim of the study was to identify miRNAs that contribute to the immunomodulatory function of human bone marrow-derived MSCs (BM-MSCs).MethodsHuman BM-MSCs were primed by coculture with activated peripheral blood mononuclear cells (aPBMCs). High throughput miRNA transcriptomic analysis was performed using Human MicroRNA TaqMan® Array Cards. The immunosuppressive function of miRNAs was investigated in mixed lymphocyte reactions and the delayed type hypersensitivity (DTH) murine model.ResultsUpon priming, 21 out of 377 tested miRNAs were significantly modulated in primed MSCs. We validated the up-regulation of miR-29a, miR-146a, miR-155 and the down-regulation of miR-149, miR-221 and miR-361 in additional samples of primed MSCs. We showed that miR-155 significantly reduced the proliferation of aPBMCs in vitro and inflammation in vivo, using the DTH model. Analysis of miRNA-mRNA interactions revealed miR-221 as a potential target gene that is down-regulated by miR-155 both in primed MSCs and in aPBMCs.ConclusionHere, we present evidence that miR-155 participates to the immunosuppressive function of human BM-MSCs and down-regulates the expression of miR-221 as a possible inflammatory mediator.

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Hackel, Alexander, Sebastian Vollmer, Kirsten Bruderek, Stephan Lang et Sven Brandau. « Immunological priming of mesenchymal stromal/stem cells and their extracellular vesicles augments their therapeutic benefits in experimental graft-versus-host disease via engagement of PD-1 ligands ». Frontiers in Immunology 14 (16 février 2023). http://dx.doi.org/10.3389/fimmu.2023.1078551.

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Mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) exert profound anti-inflammatory and regenerative effects in inflammation and tissue damage, which makes them an attractive tool for cellular therapies. In this study we have assessed the inducible immunoregulatory properties of MSCs and their EVs upon stimulation with different combinations of cytokines. First, we found that MSCs primed with IFN-γ, TNF-α and IL-1β, upregulate the expression of PD-1 ligands, as crucial mediators of their immunomodulatory activity. Further, primed MSCs and MSC-EVs, compared to unstimulated MSCs and MSC-EVs, had increased immunosuppressive effects on activated T cells and mediated an enhanced induction of regulatory T cells, in a PD-1 dependent manner. Importantly, EVs derived from primed MSCs reduced the clinical score and prolonged the survival of mice in a model of graft-versus-host disease. These effects could be reversed in vitro and in vivo by adding neutralizing antibodies directed against PD-L1 and PD-L2 to both, MSCs and their EVs. In conclusion, our data reveal a priming strategy that potentiates the immunoregulatory function of MSCs and their EVs. This concept also provides new opportunities to improve the clinical applicability and efficiency of cellular or EV-based therapeutic MSC products.

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Guo, Haiyan, Yue Su et Fang Deng. « Effects of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Lung Diseases : Current Status and Future Perspectives ». Stem Cell Reviews and Reports, 19 novembre 2020. http://dx.doi.org/10.1007/s12015-020-10085-8.

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AbstractMesenchymal stromal cells (MSCs) as a kind of pluripotent adult stem cell have shown great therapeutic potential in relation to many diseases in anti-inflammation and regeneration. The results of preclinical experiments and clinical trials have demonstrated that MSC-derived secretome possesses immunoregulatory and reparative abilities and that this secretome is capable of modulating innate and adaptive immunity and reprograming the metabolism of recipient cells via paracrine mechanisms. It has been recognized that MSC-derived secretome, including soluble proteins (cytokines, chemokines, growth factors, proteases), extracellular vesicles (EVs) and organelles, plays a key role in tissue repair and regeneration in bronchopulmonary dysplasia, acute respiratory distress syndrome (ARDS), bronchial asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension, and silicosis. This review summarizes the known functions of MSC-EV modulation in lung diseases, coupled with the future challenges of MSC-EVs as a new pharmaceutical agent. The identification of underlying mechanisms for MSC-EV might provide a new direction for MSC-centered treatment in lung diseases.Graphical abstract

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Thèses sur le sujet "Mesenchymal stromal cells, extracellular vesicles, immunoregulatory properties and inflammation"

MIDOLO, MARTINA. « Immunoregulatory properties of bone marrow mesenchymal stromal cell-derived extracellular vesicles ». Doctoral thesis, 2017. http://hdl.handle.net/11562/964970.

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Mesenchymal stromal cells (MSCs) are adult stem cells of mesodermal origin that can be isolated from various tissues, including bone marrow (BM), adipose tissue and amniotic fluid. MSCs express mesenchymal markers, i.e. CD73, CD90, and CD105, and lack expression of hematopoietic markers, such as CD45, CD34, CD11b and CD14. In addition to their tri-lineage differentiation towards adipocytes, chondrocytes and osteoblasts, MSCs modulate the immune response. In fact, MSCs can regulate the proliferation and activation of different immune effector cells (IECs), including T, B and NK cells. The biological effects of MSCs are not exclusively related to their close interaction with target cells by cell-to-cell contact, but can be mediated by molecule release. For instance, MSC immunomodulation may occur through paracrine mechanisms, including indolamine 2,3 dioxygenase, prostaglandin E2, heme-oxygenese-1, and TGF-β. In the last decade, a key mechanism of cell-to-cell communication of MSCs through extracellular vesicles (EVs) has been clarified. The potential therapeutic role of MSC-derived EVs has been described in different diseases, including cardiovascular disease, acute kidney injury, and lung injury. EVs are molecular shuttles consisting of a phospholipid bilayer containing different molecules, including proteins and different types of RNAs (mRNA and miRNA). EVs are a family of different shedding vesicles, including exosomes (EXs, 50-100 nm), microvesicles (MVs, 100-1000 nm), and apoptotic bodies (ABs, 50-500 nm). EXs originate by multivesicular body and express specific markers, such as CD63, CD9 and Alix. MVs result from the plasmatic membrane and express specific proteins of the cells of origin. To understand whether the MSC immunomodulatory effects are mediated by EV release, we characterized the protein content and immunomodulatory functions towards different immune effector cells of EVs derived from BM-MSCs. In addition, we evaluated the capability of unfractionated PBMCs to internalize MSC-derived EVs. We observed that the rate of EV internalization was higher in B cells and correlated with their capability to reduce B cell proliferation. By using a reproducible and standardized method we showed a new mechanism of MSC-mediated immunosuppression, thus characterizing better the biological function of MSC-derived EVs and paving the way to a possible clinical application of EVs as alternative cell-free therapy.

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