Extracellular Vesicles as Biomarkers and Therapeutic Tools: From Pre-Clinical to Clinical Applications

Ciferri, Maria Chiara; Quarto, Rodolfo; Tasso, Roberta

doi:10.3390/biology10050359

Cited by 123 publications

(91 citation statements)

References 77 publications

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“…It is known that EVs are vehicles of intercellular communication involved in many (patho) physiological processes. Moreover, these qualities joined to their molecular composition have positioned EVs as one of the most stable options for diagnostic and therapeutic purposes [ 34 ]. According to our data, phase F, which is the one harboring all exosomes, contains all mitochondrial markers totally stable in blood with significances among patients and controls, which makes them potential non-invasive biomarkers for RCC diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Arance

Ramírez

Rubio-Roldán

et al. 2021

Cancers

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Here, the role of non-invasive biomarkers in liquid biopsy was evaluated, mainly in exosomes and mitochondrial DNA (mtDNA) as promising, novel, and stable biomarkers for renal cell carcinoma (RCC). A total of 140 fractions (named from B to F) obtained by ultracentrifugations of whole blood samples from 28 individuals (13 patients and 15 controls) were included. Nanoparticle Tracking Analysis (NTA) was conducted to characterized exosomal fraction. Subsequently, an analysis of digital PCR (dPCR) using the QuantStudio™ 3D Digital PCR platform was performed and the quantification of mtDNA copy number by QuantStudioTM 12K Flex Real-Time PCR System (qPCR) was developed. Moreover, Next Generation Sequencing (NGS) analyses were included using MiSeq system (Illumina, San Diego, CA, USA). An F fraction, which contains all exosome data and all mitochondrial markers, was identified in dPCR and qPCR with statistically significant power (adjusted p values ≤ 0.03) when comparing cases and controls. Moreover, present analysis in mtDNA showed a relevant significance in RCC aggressiveness. To sum up, this is the first time a relation between exosomal mtDNA markers and clinical management of RCC is analyzed. We suggest a promising strategy for future liquid biopsy RCC analysis, although more analysis should be performed prior to application in routine clinical practice.

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Section: Discussionmentioning

confidence: 99%

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Arance

Ramírez

Rubio-Roldán

et al. 2021

Cancers

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“…This diverse group of biological carriers participates in various physiological and pathophysiological processes, which sparked scientific interest in recent years. Aside from being useful diagnostic and Membranes 2021, 11, 647 2 of 13 prognostic tools, which can be obtained with minimally invasive techniques [5], EV are increasingly seen as potentially privileged drug carriers [6]. Their small size and lipid bilayer confer EV the ability to travel long distances in the body, including crossing the blood-brain barrier [7] without disturbing their cargo.…”

Section: Introductionmentioning

confidence: 99%

Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles

et al. 2021

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The development and adoption of cell therapies has been largely limited by difficulties associated with their safety, handling, and storage. Extracellular vesicles (EV) have recently emerged as a likely mediator for the therapeutic effect of cells, offering several advantages over cell therapies. Due to their small size and inability to expand and metastasize, EV are generally considered safer than cell transplantation. Nevertheless, few studies have scrutinized the toxicity profile of EV, particularly after repeated high-dose administration. The present study aimed to evaluate a preparation of small EV obtained from umbilical cord blood mononuclear cells (UCB-MNC-sEV) for its cytotoxicity in different cell lines, as well as its differential accumulation, distribution, and toxicity following repeated intravenous (IV) administrations in a rodent model. In vitro, repeated sEV exposure in concentrations up to 1 × 1011 particles/mL had no deleterious impact on the viability or metabolic activity of peripheral blood mononuclear cells, THP-1 monocytes, THP-1-derived macrophages, normal dermal human fibroblasts, or human umbilical vein endothelial cells. DiR-labelled sEV, injected intravenously for four weeks in healthy rats, were detected in clearance organs, particularly the kidneys, spleen, and liver, similarly to control dye. Moreover, repeated administrations for six and twelve weeks of up to 1 × 1010 total particles of sEV dye were well-tolerated, with no changes in general haematological cell counts, or kidney and liver toxicity markers. More importantly, unlabelled sEV likewise did not induce significant alterations in cellular and biochemical blood parameters, nor any morphological changes in the heart, kidney, lung, spleen, or liver tissue. In sum, our data show that UCB-MNC-sEV have no significant toxicity in vitro or in vivo, even when administered repeatedly at high concentrations, therefore confirming their safety profile and potential suitability for future clinical use.

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“…Recent published studies suggest that EVs can be used as a prognostic/diagnostic tool for several diseases and as a therapeutic approach [70][71][72][73][74]. At the same time, it was demonstrated that cancer cells can use EVs as a mechanism to expulse chemotherapy drugs, contributing to drug resistance [75,76].…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

Martino

Rossi

Battafarano

et al. 2021

IJMS

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Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.

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Extracellular Vesicles as Biomarkers and Therapeutic Tools: From Pre-Clinical to Clinical Applications

Cited by 123 publications

References 77 publications

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles

Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

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