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Article ; Online: Extracellular vesicles in kidney disease.

Grange, Cristina / Bussolati, Benedetta

2022 Volume 18, Issue 8, Page(s) 499–513

Abstract: Extracellular vesicles are released by the majority of cell types and circulate in body fluids. They function as a long-distance cell-to-cell communication mechanism that modulates the gene expression profile and fate of target cells. Increasing evidence ...

Abstract	Extracellular vesicles are released by the majority of cell types and circulate in body fluids. They function as a long-distance cell-to-cell communication mechanism that modulates the gene expression profile and fate of target cells. Increasing evidence has established a central role of extracellular vesicles in kidney physiology and pathology. Urinary extracellular vesicles mediate crosstalk between glomerular and tubular cells and between different segments of the tubule, whereas circulating extracellular vesicles mediate organ crosstalk and are involved in the amplification of kidney damage and inflammation. The molecular profile of extracellular vesicles reflects the type and pathophysiological status of the originating cell so could potentially be exploited for diagnostic and prognostic purposes. In addition, robust preclinical data suggest that administration of exogenous extracellular vesicles could promote kidney regeneration and reduce inflammation and fibrosis in acute and chronic kidney diseases. Stem cells are thought to be the most promising source of extracellular vesicles with regenerative activity. Extracellular vesicles are also attractive candidates for drug delivery and various engineering strategies are being investigated to alter their cargo and increase their efficacy. However, rigorous standardization and scalable production strategies will be necessary to enable the clinical application of extracellular vesicles as potential therapeutics.
MeSH term(s)	Extracellular Vesicles/metabolism ; Humans ; Inflammation/metabolism ; Kidney/metabolism ; Kidney Diseases/metabolism ; Regeneration
Language	English
Publishing date	2022-05-31
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/s41581-022-00586-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Exploring the role of urinary extracellular vesicles in kidney physiology, aging, and disease progression.

Grange, Cristina / Dalmasso, Alessia / Cortez, Judiel John / Spokeviciute, Beatrice / Bussolati, Benedetta

American journal of physiology. Cell physiology

2023 Volume 325, Issue 6, Page(s) C1439–C1450

Abstract: Extracellular vesicles (EVs), membranous vesicles present in all body fluids, are considered important messengers, carrying their information over long distance and modulating the gene expression profile of recipient cells. EVs collected in urine (uEVs) ... ...

Abstract	Extracellular vesicles (EVs), membranous vesicles present in all body fluids, are considered important messengers, carrying their information over long distance and modulating the gene expression profile of recipient cells. EVs collected in urine (uEVs) are mainly originated from the apical part of urogenital tract, following the urine flow. Moreover, bacterial-derived EVs are present within urine and may reflect the composition of microbiota. Consolidated evidence has established the involvement of uEVs in renal physiology, being responsible for glomerular and tubular cross talk and among different tubular segments. uEVs may also be involved in other physiological functions such as modulation of innate immunity, coagulation, or metabolic activities. Furthermore, it has been recently remonstrated that age, sex, endurance excise, and lifestyle may influence uEV composition and release, modifying their cargo. On the other hand, uEVs appear modulators of different urogenital pathological conditions, triggering disease progression. uEVs sustain fibrosis and inflammation processes, both involved in acute and chronic kidney diseases, aging, and stone formation. The molecular signature of uEVs collected from diseased patients can be of interest for understanding kidney physiopathology and for identifying diagnostic and prognostic biomarkers.
MeSH term(s)	Humans ; Extracellular Vesicles/metabolism ; Kidney Glomerulus ; Renal Insufficiency, Chronic/metabolism ; Aging ; Disease Progression ; Biomarkers/metabolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00349.2023
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Article ; Online: Standardized Method to Functionalize Plasma-Extracellular Vesicles via Copper-Free Click Chemistry for Targeted Drug Delivery Strategies.

Ciferri, Maria Chiara / Bruno, Silvia / Rosenwasser, Nicole / Gorgun, Cansu / Reverberi, Daniele / Gagliani, Maria Cristina / Cortese, Katia / Grange, Cristina / Bussolati, Benedetta / Quarto, Rodolfo / Tasso, Roberta

ACS applied bio materials

2024 Volume 7, Issue 2, Page(s) 827–838

Abstract: Extracellular vesicles (EVs) have emerged as potential vehicles for targeted drug delivery and diagnostic applications. However, achieving consistent and reliable functionalization of EV membranes remains a challenge. Copper-catalyzed click chemistry, ... ...

Abstract	Extracellular vesicles (EVs) have emerged as potential vehicles for targeted drug delivery and diagnostic applications. However, achieving consistent and reliable functionalization of EV membranes remains a challenge. Copper-catalyzed click chemistry, commonly used for EV surface modification, poses limitations due to cytotoxicity and interference with biological systems. To overcome these limitations, we developed a standardized method for functionalizing an EV membrane via copper-free click chemistry. EVs derived from plasma hold immense potential as diagnostic and therapeutic agents. However, the isolation and functionalization of EVs from such a complex biofluid represent considerable challenges. We compared three different EV isolation methods to obtain an EV suspension with an optimal purity/yield ratio, and we identified sucrose cushion ultracentrifugation (sUC) as the ideal protocol. We then optimized the reaction conditions to successfully functionalize the plasma-EV surface through a copper-free click chemistry strategy with a fluorescently labeled azide, used as a proof-of-principle molecule. Click-EVs maintained their identity, size, and, more importantly, capacity to be efficiently taken up by responder tumor cells. Moreover, once internalized, click EVs partially followed the endosomal recycling route. The optimized reaction conditions and characterization techniques presented in this study offer a foundation for future investigations and applications of functionalized EVs in drug delivery, diagnostics, and therapeutics.
MeSH term(s)	Click Chemistry ; Drug Delivery Systems ; Extracellular Vesicles/chemistry ; Endosomes
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ISSN	2576-6422
ISSN (online)	2576-6422
DOI	10.1021/acsabm.3c00822
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine.

Pomatto, Margherita A C / Gai, Chiara / Negro, Federica / Massari, Lucia / Deregibus, Maria Chiara / Grange, Cristina / De Rosa, Francesco Giuseppe / Camussi, Giovanni

Pharmaceutics

2023 Volume 15, Issue 3

Abstract: Plant-derived extracellular vesicles (EVs) may represent a platform for the delivery of RNA-based vaccines, exploiting their natural membrane envelope to protect and deliver nucleic acids. Here, EVs extracted from orange ( ...

Abstract	Plant-derived extracellular vesicles (EVs) may represent a platform for the delivery of RNA-based vaccines, exploiting their natural membrane envelope to protect and deliver nucleic acids. Here, EVs extracted from orange (
Language	English
Publishing date	2023-03-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15030974
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Article: Immunosuppressive role of extracellular vesicles: HLA-G, an important player.

Grange, Cristina / Camussi, Giovanni

Annals of translational medicine

2017 Volume 5, Issue 10, Page(s) 223

Language	English
Publishing date	2017-05-26
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2893931-1
ISSN	2305-5847 ; 2305-5839
ISSN (online)	2305-5847
ISSN	2305-5839
DOI	10.21037/atm.2017.03.61
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Article ; Online: Potential Applications of Extracellular Vesicles in Solid Organ Transplantation.

Grange, Cristina / Bellucci, Linda / Bussolati, Benedetta / Ranghino, Andrea

Cells

2020 Volume 9, Issue 2

Abstract: Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid ... ...

Abstract	Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid organ transplantations. Mesenchymal stromal cell-derived EVs (MSC-EVs) in particular have been proposed as a new tool to improve graft survival, thanks to the modulation of tolerance toward the graft, and to their anti-fibrotic and pro-angiogenic effects. Moreover, MSC-EVs may reduce ischemia reperfusion injury, improving the recovery from acute damage. In addition, EVs currently considered helpful tools for preserving donor organs when administered before transplant in the context of hypothermic or normothermic perfusion machines. The addition of EVs to the perfusion solution, recently proposed for kidney, lung, and liver grafts, resulted in the amelioration of donor organ viability and functionality. EVs may therefore be of therapeutic interest in different aspects of the transplantation process for increasing the number of available organs and improving their long-term survival.
MeSH term(s)	Animals ; Extracellular Vesicles/metabolism ; Graft vs Host Disease/metabolism ; Humans ; Organ Transplantation ; Perfusion ; Regenerative Medicine ; Stem Cells/metabolism
Language	English
Publishing date	2020-02-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9020369
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Article: Urine-derived podocytes from steroid resistant nephrotic syndrome patients as a model for renal-progenitor derived extracellular vesicles effect and drug screening.

Tanzi, Adele / Buono, Lola / Grange, Cristina / Iampietro, Corinne / Brossa, Alessia / Arcolino, Fanny Oliveira / Arigoni, Maddalena / Calogero, Raffaele / Perin, Laura / Deaglio, Silvia / Levtchenko, Elena / Peruzzi, Licia / Bussolati, Benedetta

Research square

2024

Abstract: Background: Personalized disease models are crucial for assessing the specific response of diseased cells to drugs, particularly novel biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular ... ...

Abstract	Background: Personalized disease models are crucial for assessing the specific response of diseased cells to drugs, particularly novel biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular communication, have gained therapeutic interest due to their ability to reprogram target cells. We here utilized urinary podocytes obtained from children affected by steroid-resistant nephrotic syndrome with characterized genetic mutations as a model to test the therapeutic potential of EVs derived from kidney progenitor cells. Methods: EVs were isolated from kidney progenitor cells (nKPCs) derived from the urine of a preterm neonate. Three lines of urinary podocytes obtained from nephrotic patients' urine and a line of Alport patient podocytes were characterized and used to assess albumin permeability in response to various drugs or to nKPC-EVs. RNA sequencing was conducted to identify commonly modulated pathways. Results: Podocytes appeared unresponsive to pharmacological treatments, except for a podocyte line demonstrating responsiveness, in alignment with the patient's clinical response at 48 months. At variance, treatment with the nKPC-EVs was able to significantly reduce permeability in all the steroid-resistant patients-derived podocytes as well as in the line of Alport-derived podocytes. RNA sequencing of nKPC-EV-treated podocytes revealed the common upregulation of two genes (small ubiquitin-related modifier 1 (SUMO1) and Sentrin-specific protease 2 (SENP2)) involved in the SUMOylation pathway, a process recently demonstrated to play a role in slit diaphragm stabilization. Gene ontology analysis on podocyte expression profile highlighted cell-to-cell adhesion as the primary upregulated biological activity in treated podocytes. Conclusions: nKPCs emerge as a promising non-invasive source of EVs with potential therapeutic effects on podocyte dysfunction. Furthermore, our findings suggest the possibility of establishing a non-invasive in vitro model for screening regenerative compounds on patient-derived podocytes.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3959549/v1
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Article ; Online: Potential Applications of Extracellular Vesicles in Solid Organ Transplantation

Cristina Grange / Linda Bellucci / Benedetta Bussolati / Andrea Ranghino

Cells, Vol 9, Iss 2, p

2020 Volume 369

Abstract	Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid organ transplantations. Mesenchymal stromal cell-derived EVs (MSC-EVs) in particular have been proposed as a new tool to improve graft survival, thanks to the modulation of tolerance toward the graft, and to their anti-fibrotic and pro-angiogenic effects. Moreover, MSC-EVs may reduce ischemia reperfusion injury, improving the recovery from acute damage. In addition, EVs currently considered helpful tools for preserving donor organs when administered before transplant in the context of hypothermic or normothermic perfusion machines. The addition of EVs to the perfusion solution, recently proposed for kidney, lung, and liver grafts, resulted in the amelioration of donor organ viability and functionality. EVs may therefore be of therapeutic interest in different aspects of the transplantation process for increasing the number of available organs and improving their long-term survival.
Keywords	exosomes ; regenerative medicine ; machinery perfusion ; transplant ; preconditioning ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Extracellular Vesicles and Carried miRNAs in the Progression of Renal Cell Carcinoma.

Grange, Cristina / Brossa, Alessia / Bussolati, Benedetta

International journal of molecular sciences

2019 Volume 20, Issue 8

Abstract: The formation and maintenance of renal cell carcinomas (RCC) involve many cell types, such as cancer stem and differentiated cells, endothelial cells, fibroblasts and immune cells. These all contribute to the creation of a favorable tumor ... ...

Abstract	The formation and maintenance of renal cell carcinomas (RCC) involve many cell types, such as cancer stem and differentiated cells, endothelial cells, fibroblasts and immune cells. These all contribute to the creation of a favorable tumor microenvironment to promote tumor growth and metastasis. Extracellular vesicles (EVs) are considered to be efficient messengers that facilitate the exchange of information within the different tumor cell types. Indeed, tumor EVs display features of their originating cells and force recipient cells towards a pro-tumorigenic phenotype. This review summarizes the recent knowledge related to the biological role of EVs, shed by renal tumor cells and renal cancer stem cells in different aspects of RCC progression, such as angiogenesis, immune escape and tumor growth. Moreover, a specific role for renal cancer stem cell derived EVs is described in the formation of the pre-metastatic niche. We also highlight the tumor EV cargo, especially the oncogenic miRNAs, which are involved in these processes. Finally, the circulating miRNAs appear to be a promising source of biomarkers in RCC.
MeSH term(s)	Biomarkers ; Cancer-Associated Fibroblasts/metabolism ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/metabolism ; Carcinoma, Renal Cell/pathology ; Circulating MicroRNA ; Disease Progression ; Extracellular Vesicles/metabolism ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism ; Kidney Neoplasms/pathology ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Neoplastic Stem Cells/metabolism ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/metabolism ; Stromal Cells/metabolism ; Tumor Microenvironment/genetics
Chemical Substances	Biomarkers ; Circulating MicroRNA ; MicroRNAs
Language	English
Publishing date	2019-04-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20081832
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Stem Cell-Derived Extracellular Vesicles and Kidney Regeneration.

Grange, Cristina / Skovronova, Renata / Marabese, Federica / Bussolati, Benedetta

Cells

2019 Volume 8, Issue 10

Abstract: Extracellular vesicles (EVs) are membranous vesicles containing active proteins, lipids, and different types of genetic material such as miRNAs, mRNAs, and DNAs related to the characteristics of the originating cell. They possess a distinctive capacity ... ...

Abstract	Extracellular vesicles (EVs) are membranous vesicles containing active proteins, lipids, and different types of genetic material such as miRNAs, mRNAs, and DNAs related to the characteristics of the originating cell. They possess a distinctive capacity to communicate over long distances. EVs have been involved in the modulation of several pathophysiological conditions and, more importantly, stem cell-derived EVs appear as a new promising therapeutic option. In fact, several reports provide convincing evidence of the regenerative potential of EVs released by stem cells and, in particular, mesenchymal stromal cells (MSCs) in different kidney injury models. Described mechanisms involve the reprogramming of injured cells, cell proliferation and angiogenesis, and inhibition of cell apoptosis and inflammation. Besides, the therapeutic use of MSC-EVs in clinical trials is under investigation. This review will focus on MSC-EV applications in preclinical models of acute and chronic renal damage including recent data on their use in kidney transplant conditioning. Moreover, ongoing clinical trials are described. Finally, new strategies to broaden and enhance EV therapeutic efficacy by engineering are discussed.
MeSH term(s)	Animals ; Cellular Reprogramming ; Clinical Trials as Topic ; Disease Models, Animal ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/transplantation ; Humans ; Kidney/physiology ; Kidney Diseases/therapy ; Kidney Transplantation ; Mesenchymal Stem Cells/cytology ; Regeneration ; Transplantation Conditioning
Language	English
Publishing date	2019-10-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells8101240
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