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

2022 ◽  
Vol 12 ◽  
Author(s):  
Yunwei Zhang ◽  
Xiaofei Zhang ◽  
Hongji Zhang ◽  
Peng Song ◽  
Wenming Pan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hemorrhagic Shock ◽  
Extracellular Vesicles ◽  
Kupffer Cells ◽  
Hepatic Injury ◽  
Interleukin 10 ◽  
Cell Polarization ◽  
Anti Inflammatory ◽  
Traumatic Hemorrhagic Shock

Traumatic hemorrhagic shock (THS) is a major cause of mortality and morbidity worldwide in severely injured patients. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and tissue repair potential mainly through a paracrine pathway mediated by MSC-derived extracellular vesicles (MSC-EVs). Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine that plays a crucial role during the inflammatory response, with a broad range of effects on innate and adaptive immunity, preventing damage to the host and maintaining normal tissue homeostasis. However, the function and mechanism of IL-10 in MSC-mediated protective effect in THS remain obscure. Here, we show that MSCs significantly attenuate hepatic injury and inflammation from THS in mice. Notably, these beneficial effects of MSCs disappeared when IL-10 was knocked out in EVs or when recombinant IL-10 was administered to mice. Mechanistically, MSC-EVs function to carry and deliver IL-10 as cargo. WT MSC-EVs restored the function of IL-10 KO MSCs during THS injury. We further demonstrated that EVs containing IL-10 mainly accumulated in the liver during THS, where they were captured by Kupffer cells and induced the expression of PTPN22. These effects subsequently shifted Kupffer cells to an anti-inflammatory phenotype and mitigated liver inflammation and injury. Therefore, our study indicates that MSC-EVs containing IL-10 alleviate THS-induced hepatic injury and may serve as a cell-free therapeutic approach for THS.

scholarly journals Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

2021 ◽  
Vol 22 (3) ◽  
pp. 1375
Author(s):  
María Carmen Carceller ◽  
María Isabel Guillén ◽  
María Luisa Gil ◽  
María José Alcaraz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Nuclear Factor Κb ◽  
Peritoneal Macrophages ◽  
Toll Like Receptor 4 ◽  
Anti Inflammatory ◽  
Phagocytic Response

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

Angiogenic and anti-inflammatory properties of mesenchymal stem cells from cord blood: soluble factors and extracellular vesicles for cell regeneration

2016 ◽  
Vol 95 (6-7) ◽  
pp. 228-238 ◽  
Author(s):  
Tiziana Montemurro ◽  
Mariele Viganò ◽  
Enrico Ragni ◽  
Mario Barilani ◽  
Valentina Parazzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cord Blood ◽  
Extracellular Vesicles ◽  
Cell Regeneration ◽  
Soluble Factors ◽  
Anti Inflammatory

scholarly journals Development of Hydrogel with Anti-Inflammatory Properties Permissive for the Growth of Human Adipose Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
R. Sánchez-Sánchez ◽  
E. Martínez-Arredondo ◽  
V. Martínez-López ◽  
Y. Melgarejo-Ramírez ◽  
A. Brena-Molina ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wound Repair ◽  
Inflammatory Cytokine ◽  
Type I Collagen ◽  
Interleukin 10 ◽  
Tissue Type ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

Skin wound repair requires the development of different kinds of biomaterials that must be capable of restoring the damaged tissue. Type I collagen and chitosan have been widely used to develop scaffolds for skin engineering because of their cell-related signaling properties such as proliferation, migration, and survival. Collagen is the major component of the skin extracellular matrix (ECM), while chitosan mimics the structure of the native polysaccharides and glycosaminoglycans in the ECM. Chitosan and its derivatives are also widely used as drug delivery vehicles since they are biodegradable and noncytotoxic. Regulation of the inflammatory response is crucial for wound healing and tissue regeneration processes; and, consequently, the development of biomaterials such as hydrogels with anti-inflammatory properties is very important and permissive for the growth of cells. In the last years, it has been shown that mesenchymal stem cells have clinical importance in the treatment of different pathologies, for example, skin injuries. In this paper, we describe the anti-inflammatory activity of collagen type 1/chitosan/dexamethasone hydrogel, which is permissive for the culture of human adipose-derived mesenchymal stem cells (hADMSC). Our results show that hADMSC cultured in the hydrogel are viable, proliferate, and secrete the anti-inflammatory cytokine interleukin-10 (IL-10) but not the inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α).

scholarly journals Mesenchymal Stem Cell–Derived Extracellular Vesicles Induce Regulatory T Cells to Ameliorate Chronic Kidney Injury

Hypertension ◽  
2020 ◽  
Vol 75 (5) ◽  
pp. 1223-1232 ◽  
Author(s):  
Turun Song ◽  
Alfonso Eirin ◽  
Xiangyang Zhu ◽  
Yu Zhao ◽  
James D. Krier ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Extracellular Vesicles ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Activated T Cells ◽  
Anti Inflammatory

Metabolic syndrome (MetS) profoundly changes the contents of mesenchymal stem cells and mesenchymal stem cells–derived extracellular vesicles (EVs). The anti-inflammatory TGF-β (transforming growth factor-β) is selectively enriched in EVs from Lean but not from MetS pigs, but the functional impact of this endowment remains unknown. We hypothesized that Lean-EVs more effectively induce regulatory T cells in injured kidneys. Five groups of pigs (n=7 each) were studied after 16 weeks of diet-induced MetS and unilateral renal artery stenosis (RAS; MetS+RAS). Two groups of MetS+RAS were treated 4 weeks earlier with an intrarenal injection of either Lean-EVs or MetS-EVs. MetS+RAS had lower renal volume, renal blood flow, and glomerular filtration rate than MetS pigs. Compared with Lean-EVs, MetS-EVs were less effective in improving renal function and decreasing tubular injury and fibrosis in MetS+RAS. Lean-EVs upregulated TGF-β expression in stenotic kidney and increased regulatory T cells numbers more prominently. Furthermore, markedly upregulated anti-inflammatory M2 macrophages reduced proinflammatory M1 macrophages, and CD8 + T cells were detected in stenotic kidneys treated with Lean-EVs compared with MetS-EVs, and renal vein levels of interleukin-1β were reduced. In vitro, coculture of Lean-EVs with activated T cells led to greater TGF-β-dependent regulatory T cells induction than did MetS-EVs. Therefore, the beneficial effects of mesenchymal stem cells–derived EVs on injured kidneys might be partly mediated by their content of TGF-β signaling components, which permitting increased Treg preponderance. Modulating EV cargo and transforming their functionality might be useful for renal repair.

scholarly journals Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes

2018 ◽  
Vol 47 (1) ◽  
pp. 11-25 ◽  
Author(s):  
Miguel Tofiño-Vian ◽  
Maria Isabel Guillén ◽  
María Dolores Pérez del Caz ◽  
Antonio Silvestre ◽  
María José Alcaraz
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Prostaglandin E ◽  
No Production ◽  
Oa Chondrocytes ◽  
Anti Inflammatory

Background/Aims: Chronic inflammation contributes to cartilage degeneration during the progression of osteoarthritis (OA). Adipose tissue-derived mesenchymal stem cells (AD-MSC) show great potential to treat inflammatory and degradative processes in OA and have demonstrated paracrine effects in chondrocytes. In the present work, we have isolated and characterized the extracellular vesicles from human AD-MSC to investigate their role in the chondroprotective actions of these cells. Methods: AD-MSC were isolated by collagenase treatment from adipose tissue from healthy individuals subjected to abdominal lipectomy surgery. Microvesicles and exosomes were obtained from conditioned medium by filtration and differential centrifugation. Chondrocytes from OA patients were used in primary culture and stimulated with 10 ng/ml interleukin(IL)-1β in the presence or absence of AD-MSC microvesicles, exosomes or conditioned medium. Protein expression was investigated by ELISA and immunofluorescence, transcription factor-DNA binding by ELISA, gene expression by real-time PCR, prostaglandin E2 (PGE2) by radioimmunoassay, and matrix metalloproteinase (MMP) activity and nitric oxide (NO) production by fluorometry. Results: In OA chondrocytes stimulated with IL-1β, microvesicles and exosomes reduced the production of inflammatory mediators tumor necrosis factor-α, IL-6, PGE2 and NO. The downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 would lead to the decreased PGE2 production while the effect on NO could depend on the reduction of inducible nitric oxide synthase expression. Treatment of OA chondrocytes with extracellular vesicles also decreased the release of MMP activity and MMP-13 expression whereas the production of the anti-inflammatory cytokine IL-10 and the expression of collagen II were significantly enhanced. The reduction of inflammatory and catabolic mediators could be the consequence of a lower activation of nuclear factor-κB and activator protein-1. The upregulation of annexin A1 specially in MV may contribute to the anti-inflammatory and chondroprotective effects of AD-MSC. Conclusions: Our data support the interest of AD-MSC extracellular vesicles to develop new therapeutic approaches in joint conditions.

The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment

2020 ◽  
Vol 15 (7) ◽  
pp. 623-638
Author(s):  
Saeideh Gholamzadeh Khoei ◽  
Fateme Karimi Dermani ◽  
Sara Malih ◽  
Nashmin Fayazi ◽  
Mohsen Sheykhhasan
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Adult Stem Cells ◽  
Heart Diseases ◽  
Therapeutic Option ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Cellular Source

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusions: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

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