5,023 research outputs found
Release of MicroRNA-Containing Vesicles Can Stimulate Angiogenesis and Metastasis in Renal Carcinoma
No full textRenal cell carcinoma is a common form of urologic tumor, with low incidence but a high metastatic rate at diagnosis and high frequency of relapse. Renal cell carcinoma comprises a heterogeneous group of subtypes, classified according to their histopathological features and clinical behavior. Diagnostic approaches used to identify malignant tissue are based on immunohistochemical techniques. However, new molecular methods have been recently proposed for profiling and staging renal tumors based on their microRNA (miRNAs) expression. In fact, miRNAs have been shown to have abnormal levels in many cancers compared with their normal tissue counterparts. For this reason, along with the fact that they are present in biological fluids, miRNAs could serve as a useful diagnostic tool. Moreover, miRNAs may modify the translational profile of cells through direct degradation of their target mRNAs or by blocking their translation into functional proteins. The biological function of secretory miRNAs requires protection from extracellular degrading enzymes, which is achieved by envelopment of miRNAs within extracellular vesicles (EVs), which are subsequently secreted. EVs are a heterogeneous population of vesicles that includes shedding vesicles and exosomes, and are variable in size, composition, and releasing mechanisms. Following uptake, EVs are able to induce epigenetic modifications in target cells by the transfer of active proteins, lipids, RNA, and miRNAs. Therefore, through the transfer of selected miRNAs, tumor-released EVs may provide oncogenic signals to stromal cells. In particular, EVs released from renal carcinoma stem cells contain miRNAs that are potentially involved in triggering angiogenesis and metastasis
Role of stem-cell-derived microvesicles in the paracrine action of stem cells
No full textThe paracrine theory has recently changed the view of the biological action of stem cells and of the subsequent potential application of stem cells in regenerative medicine. Indeed, most of the beneficial effects of stem-cell-based therapy have been attributed to soluble factors released from stem cells. In this context, MVs (microvesicles) released as exosomes from the endosomal compartment, or as shedding vesicles from the cell surface, may play a relevant role in the intercellular communication between stem and injured cells. By transferring proteins, bioactive lipids, mRNA and microRNA, MVs act as vehicles of information that may lead to alteration of the phenotype of recipient cells. The exchange of information between stem cells and tissue-injured cells is reciprocal. The MV-mediated transfer of tissue-specific information from the injured cells to stem cells may reprogramme the latter to gain phenotypic and functional characteristics of the cell of origin. On the other hand, MVs released from stem cells may confer a stem-cell-like phenotype to injured cells, with the consequent activation of self-regenerative programmes. In fact, MVs released from stem cells retain several biological activities that are able to reproduce the beneficial effects of stem cells in a variety of experimental models
Use of microvesicles (MVS) for preparing a medicament having adjuvant activity on endothelial cell transplantation, particularlly in the treatment of diabetes by pancreatic islet transplantation, and related method
No full textThe invention relates to the use of microvesicles derived from cells of the endothelial cell lineage, preferably from endothelial progenitor cells, as an adjuvant agent in endothelial cell-pancreatic islet transplantation, particularly in the treatment of type I or type II diabetes by pancreatic islet transplantation. The adjuvant effect of the microvesicles consists in the improvement of survival and functionality of the transplanted islets. The adjuvant effect of the microvesicles is maintained even when the recipient is subjected to rapamycin-based immunosuppression
Mesenchymal stem cells derived extracellular vesicles for chronic kidney disease: pleiotropic mechanisms of actions of a versatile therapy
No full textChronic kidney disease (CKD) has increasingly become a major health concern worldwide, globally affecting 10%–15% of adults, with significant implications for morbidity and mortality. This progressive condition can potentially evolve into end-stage renal disease (ESRD), requiring dialysis or renal transplant. However, the heaviest impact of CKD is due to an associated increased cardiovascular risk, due to frequently coexisting hypertension and diabetes and non-traditional risk factors, including accumulation of atherogenic toxins, alteration of calcium-phosphate balance, oxidative stress and chronic microinflammation. Mesenchymal stem cells (MSCs) have been proposed as a therapy for CKD due to their immunomodulating and tissue repairing properties. It has been proposed that extracellular vesicles (EVs) may mediate the therapeutic effects of the cells of origin and MSC-EVs have shown promise as treatment of different aspects of CKD in experimental settings. Their anti-fibrotic and anti-apoptotic properties may inhibit progression of CKD and promote healing of tubular and glomerular damage. MSC-EVs can prevent epithelial-mesenchymal transition, a key mechanism of evolution of acute kidney injury towards CKD. These actions may inhibit development of interstitial fibrosis and accumulation of the extracellular matrix components (ECM), key lesions which promote the progression of CKD. Furthermore, MSC-EVs also exert anti-inflammatory and anti-oxidant properties which may reduce vascular damage and cardiovascular risk associated with CKD. For example, Human Liver Stem Cell (HLSC)-derived EVs (HLSC-EVs) can reverse renal and cardiac alterations. As shown in a murine model of partial nephrectomy, HLSC-EVs shuttled proteases with ECM remodeling activity, lending support to the possibility of a simultaneous cardio-nephroprotective effect. Adipose, umbilical cord and inducible- MSCs are other possible sources of EVs potentially applicable to obtain reparative processes in CKD and ESRD. Overall, building experimental evidence suggests that MSC-EVs derived from different sources are a promising therapeutic tool to prevent development and progression of CKD and to reduce related cardiovascular risk. The strength of this therapy lies in its multi-level and pleiotropic actions which appear to interfere with many key etiopathogenetic mechanisms of CKD. Interesting future perspective is a combined therapy associating MSC-EVs with drugs to achieve synergistic effects and recent finding indicate the feasibility of this approach
Use of microvesicles (MVS) derived from stem cells for preparing a medicament for endo/epithelial regeneration of damaged or injured tissues or organs, and related in vitro and in vivo methods
No full textThe invention relates to the use of microvesicles (MVs) derived from stem cells for preparing a medicament for the endo/epithelial regeneration of damaged tissues or organs and/or for inhibiting the apoptosis induced by cytostatic agents. The stem cell from which the microvesicles are obtained is preferably selected from the group consisting of endothelial progenitor cells (EPCs), mesenchimal stem cells (MSCs), renal progenitors CDl 33+, adult human liver stem cells (HLSC) and any combination thereof. The microvesicles may be used in both in vitro and in vivo applications, such as for example the regeneration of damaged tissues or organs and the treatment of renal injury and hepatic injury, particularly acute renal failure (ARF) and acute hepatic failure (AHF)
Extracellular vesicles derived from renal cancer stem cells induce a pro-tumorigenic phenotype in mesenchymal stromal cells
No full textRenal carcinomas have been shown to contain a population of cancer stem cells (CSCs) that present self-renewing capacity and support tumor growth and metastasis. CSCs were shown to secrete large amount of extracellular vesicles (EVs) that can transfer several molecules (proteins, lipids and nucleic acids) and induce epigenetic changes in target cells. Mesenchymal Stromal Cells (MSCs) are susceptible to tumor signalling and can be recruited to tumor regions. The precise role of MSCs in tumor development is still under debate since both pro- and anti-tumorigenic effects have been reported. In this study we analysed the participation of renal CSC-derived EVs in the interaction between tumor and MSCs. We found that CSC-derived EVs promoted persistent phenotypical changes in MSCs characterized by an increased expression of genes associated with cell migration (CXCR4, CXCR7), matrix remodeling (COL4A3), angiogenesis and tumor growth (IL-8, Osteopontin and Myeloperoxidase). EV-stimulated MSCs exhibited in vitro an enhancement of migration toward the tumor conditioned medium. Moreover, EV-stimulated MSCs enhanced migration of renal tumor cells and induced vessel-like formation. In vivo, EV-stimulated MSCs supported tumor development and vascularization, when co-injected with renal tumor cells. In conclusion, CSC-derived EVs induced phenotypical changes in MSCs that are associated with tumor growth
Le «buone letture». 2. Giovanni Casati
No full textIl saggio è costituito da due parti, la prima delle quali, dedicata alla fondazione della Federazione italiana delle biblioteche circolanti cattoliche, è stata pubblicata nel precedente numero dei «Nuovi Annali», XXVII (2013), pp. 137-163. In questa seconda parte viene delineata la figura intellettuale di Giovanni Casati, che diresse la «Rivista di letture» dal 1912 al 1944, trasformando il periodico della Federazione in una rivista impegnata nella divulgazione della cultura cattolica. A questo impegno militante Casati fece corrispondere un intenso programma editoriale, che trovò espressione nella pubblicazione di saggi letterari, di manuali e opere repertoriali.The study consists of two parts; the first is dedicated to the history of the Federazione italiana delle biblioteche circolanti cattoliche since its foundation (1904) up to 1912 and was published in the previous volume of the «Nuovi Annali », XXVII (2013), pp. 137-163. In this second part, the author outlines the intellectual figure of Giovanni Casati, who directed the «Rivista di letture» from 1912 to 1944, transforming the magazine of the Federation in a journal engaged in the spreading of Catholic culture. To this militant engagement Casati matched an intense publishing program, which found its expression in the publication of literary essays, manuals and reference works
Mesenchymal Stromal Cells Epithelial Transition Induced by Renal Tubular Cells-Derived Extracellular Vesicles.
No full textMesenchymal-epithelial interactions play an important role in renal tubular morphogenesis and in maintaining the structure of the kidney. The aim of this study was to investigate whether extracellular vesicles (EVs) produced by human renal proximal tubular epithelial cells (RPTECs) may induce mesenchymal-epithelial transition of bone marrow-derived mesenchymal stromal cells (MSCs). To test this hypothesis, we characterized the phenotype and the RNA content of EVs and we evaluated the in vitro uptake and activity of EVs on MSCs. MicroRNA (miRNA) analysis suggested the possible implication of the miR-200 family carried by EVs in the epithelial commitment of MSCs. Bone marrow-derived MSCs were incubated with EVs, or RPTEC-derived total conditioned medium, or conditioned medium depleted of EVs. As a positive control, MSCs were co-cultured in a transwell system with RPTECs. Epithelial commitment of MSCs was assessed by real time PCR and by immunofluorescence analysis of cellular expression of specific mesenchymal and epithelial markers. After one week of incubation with EVs and total conditioned medium, we observed mesenchymal-epithelial transition in MSCs. Stimulation with conditioned medium depleted of EVs did not induce any change in mesenchymal and epithelial gene expression. Since EVs were found to contain the miR-200 family, we transfected MSCs using synthetic miR-200 mimics. After one week of transfection, mesenchymal-epithelial transition was induced in MSCs. In conclusion, miR-200 carrying EVs released from RPTECs induce the epithelial commitment of MSCs that may contribute to their regenerative potential. Based on experiments of MSC transfection with miR-200 mimics, we suggested that the miR-200 family may be involved in mesenchymal-epithelial transition of MSCs
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