scholarly journals Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Miguel Tofiño-Vian ◽  
Maria Isabel Guillén ◽  
María Dolores Pérez del Caz ◽  
Miguel Angel Castejón ◽  
Maria José Alcaraz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Prostaglandin E ◽  
Protective Effects ◽  
Relevant Factor ◽  
Paracrine Effects ◽  
Inflammatory Stress ◽  
And Oxidative Stress

Osteoarthritis (OA) affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC) are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin- (IL-) 1βindicate that conditioned medium, microvesicles, and exosomes from ASC downregulate senescence-associatedβ-galactosidase activity and the accumulation ofγH2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E2. The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects.

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.

Bone mesenchymal stem cells derived extracellular vesicles promotes TRAIL-related apoptosis of hepatocellular carcinoma cells via the delivery of microRNA-20a-3p

2020 ◽  
pp. 1-13
Author(s):  
Lu Deng ◽  
Chang Wang ◽  
Chao He ◽  
Li Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Cell Apoptosis ◽  
Bone Mesenchymal Stem Cells ◽  
Hcc Cells

OBJECTIVE: Bone mesenchymal stem cells (BMSCs) have been widely researched in cancer treatment, including hepatocellular carcinoma (HCC). This study intended to discuss the mechanism of miR-20a-3p in BMSCs-extracellular vesicles (EVs) in HCC apoptosis. METHODS: BMSCs were isolated and identified. EVs derived from BMSCs were extracted and identified. After overexpressing or inhibiting miR-20a-3p expression in BMSCs, EVs were extracted and acted on HCC cells and transplanted tumors. HCC cell apoptosis in the treatment of BMSCs-conditioned medium, BMSCs-EVs and/or miR-20a-3p mimic/inhibitor were evaluated, with the detection of levels of TRAIL and TRAIL-related proteins. A functional rescue experiment about c-FLIP was carried out in HCC cells. The target binding relationship between miR-20a-3p and c-FLIP was detected. The subcutaneous tumorigenesis model of mice was established and injected with BMSCs-EVs to estimate the effect of BMSCs-EVs-miR-20a-3p on HCC growth. RESULTS: EVs isolated from BMSCs conditioned medium promoted the apoptosis of HCC cells. After BMSCs-EVs treatment, TRAIL levels, downstream proteins and miR-20a-3p were increased significantly, but the expression of c-FLIP was decreased. miR-20a-3p could target c-FLIP. BMSCs-EVs inhibited the growth of HCC cells, decreased c-FLIP expression, increased TRAIL levels, and promote the of HCC cell apoptosis. BMSCs-EVs with overexpressing miR-20a-3p further enhanced the apoptotic effect of HCC cells in vitro and in vivo. CONCLUSION: BMSCs-EVs-carried miR-20a-3p targets c-FLIP and increases TRAIL levels in HCC cells, thus promoting TRAIL-related apoptosis.

scholarly journals Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes

Aging ◽  
2016 ◽  
Vol 8 (8) ◽  
pp. 1703-1717 ◽  
Author(s):  
Julia Platas ◽  
Maria Isabel Guillén ◽  
Maria Dolores Pérez del Caz ◽  
Francisco Gomar ◽  
Miguel Angel Castejón ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Paracrine Effects ◽  
Inflammatory Stress ◽  
Osteoarthritic Chondrocytes

scholarly journals Could the Enrichment of a Biomaterial with Conditioned Medium or Extracellular Vesicles Modify Bone-Remodeling Kinetics during a Defect Healing? Evaluations on Rat Calvaria with Synchrotron-Based Microtomography

2020 ◽  
Vol 10 (7) ◽  
pp. 2336
Author(s):  
Alessandra Giuliani ◽  
Gabriela Sena ◽  
Giuliana Tromba ◽  
Emanuela Mazzon ◽  
Antonella Fontana ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Conditioned Medium ◽  
Bone Remodeling ◽  
Extracellular Vesicles ◽  
Bone Tissue Regeneration ◽  
Bone Mass Density ◽  
Defect Healing ◽  
Defect Site

Tissue engineering has been shown to offer promising approaches for bone regeneration, mostly based on replacement with biomaterials that provide specific environments and support for bone growth. In this context, we previously showed that mesenchymal stem cells (MSCs) and their derivatives, such as conditioned medium (CM) and extracellular vesicles (EV), when seeded on collagen membranes (COL) or polylactide (PLA) biomaterials, are able to favor bone tissue regeneration, especially evidenced in animal model calvary defects. In the present study, we investigated whether the enrichment of a rat calvary defect site with CM, EVs and polyethylenimine (PEI)-engineered EVs could substantially modify the bone remodeling kinetics during defect healing, as these products were reported to favor bone regeneration. In particular, we focused the study, performed by synchrotron radiation-based high-resolution tomography, on the analysis of the bone mass density distribution. We proved that the enrichment of a defect site with CM, EVs and PEI-EVs substantially modifies, often accelerating, bone remodeling kinetics and the related mineralization process during defect healing. Moreover, different biomaterials (COL or PLA) in combination with stem cells of different origin (namely, human periodontal ligament stem cells-hPDLSCs and human gingival mesenchymal stem cells-hGMSCs) and their own CM, EVs and PEI-EVs products were shown to exhibit different mineralization kinetics.

scholarly journals Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryo Kanai ◽  
Ayumu Nakashima ◽  
Shigehiro Doi ◽  
Tomoe Kimura ◽  
Ken Yoshida ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Prostaglandin E2 ◽  
Conditioned Medium ◽  
Renal Fibrosis ◽  
Interferon Γ ◽  
Prostaglandin E ◽  
Therapeutic Effects ◽  
Control Mscs ◽  
Ifn Γ

AbstractMesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs’ therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia–reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-β1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.

scholarly journals Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1

2011 ◽  
Vol 300 (1) ◽  
pp. F254-F262 ◽  
Author(s):  
Abolfazl Zarjou ◽  
Junghyun Kim ◽  
Amie M. Traylor ◽  
Paul W. Sanders ◽  
József Balla ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Conditioned Medium ◽  
Heme Oxygenase ◽  
Morphological Changes ◽  
Heme Oxygenase 1 ◽  
Paracrine Effects ◽  
Angiogenic Potential ◽  
Promising Therapeutic Approach

Multipotent mesenchymal stem cells (MSC) have become a popular and promising therapeutic approach in many clinical conditions. MSC are beneficial in animal models of acute kidney injury (AKI), by mediating differentiation-independent paracrine properties, and have prompted ongoing clinical trials to evaluate the safety and efficacy of MSC. Heme oxygenase-1 (HO-1) is induced in response to stress including AKI and has important anti-apoptotic, anti-inflammatory, and proangiogenic properties in these settings. We therefore examined whether HO-1 plays a role in the beneficial effects of MSC in AKI. We isolated MSC from bone marrow of age-matched HO-1+/+ and HO-1−/− mice. Our studies indicate that while differentiation of MSC into osteo- and adipocytic lineages did not differ between cells isolated from HO-1+/+ and HO-1−/− mice, MSC from HO-1−/− mice had significantly lower angiogenic potential. Moreover, HO-1−/− MSC demonstrated reduced expression and secretion of several important growth and proangiogenic factors (stromal cell-derived factor-1, vascular endothelial growth factor-A, and hepatocyte growth factor) compared with MSC derived from HO-1+/+ mice. In addition, conditioned medium of HO-1+/+ MSC rescued functional and morphological changes associated with cisplatin-induced AKI, while the HO-1−/−-conditioned medium was ineffectual. Our studies indicate that HO-1 plays an important role in MSC-mediated protection. The results expand understanding of the renoprotective effects of MSC and may provide novel strategies to better utilize MSC in various disease models.

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