Maria Chiara Deregibus

Maria Chiara Deregibus
University of Turin | UNITO · Department of Medical Science

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129
Publications
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Publications

Publications (129)
Preprint
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Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of E...
Article
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mRNA-based vaccines were effective in contrasting SARS-CoV-2 infection. However, they presented several limitations of storage and supply chain, and their parenteral administration elicited a limited mucosal IgA immune response. Extracellular vesicles (EVs) have been recognized as a mechanism of cell-to-cell communication well-preserved in all life...
Article
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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 (Citrus sinensis) juice (oEVs) were investigated as carriers for oral and intranasal SARS-CoV-2 mRNA vaccine. oEVs were efficient...
Article
Extracellular vesicles (EVs) are double membrane vesicles, abundant in all biological fluids. However, the characterization of EVs in aqueous humor (AH) is still limited. The aim of the present work was to characterize EVs isolated from AH (AH-EVs) in terms of surface markers of cellular origin and functional properties. We obtained AHs from patien...
Article
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Extracellular vesicles form a complex intercellular communication network, shuttling a variety of proteins, lipids, and nucleic acids, including regulatory RNAs, such as microRNAs. Transfer of these molecules to target cells allows for the modulation of sets of genes and mediates multiple paracrine and endocrine actions. EVs exert broad pro-inflamm...
Article
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Extracellular vesicles (EVs) and viruses share common features: size, structure, biogenesis and uptake. In order to generate EVs expressing the SARS-CoV-2 spike protein on their surface (S-EVs), we collected EVs from SARS-CoV-2 spike expressing human embryonic kidney (HEK-293T) cells by stable transfection with a vector coding for the S1 and S2 sub...
Article
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Extracellular vesicles released by mesenchymal stromal cells (MSC-EVs) are a promising resource for regenerative medicine. Small MSC-EVs represent the active EV fraction. A bulk analysis was applied to characterise MSC-EVs’ identity and purity, with the assessment of single EV morphology, size and integrity using electron microscopy. We applied dif...
Article
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Human liver stem-cell-derived extracellular vesicles (HLSC-EVs) exhibit therapeutic properties in various pre-clinical models of kidney injury. We previously reported an overall improvement in kidney function following treatment with HLSC-EVs in a model of aristolochic acid nephropathy (AAN). Here, we provide evidence that HLSC-EVs exert anti-fibro...
Preprint
Full-text available
Extracellular vesicles released by mesenchymal stromal cells (MSC EVs) are a promising resource for regenerative medicine. In particular, small MSC EVs represent the active EV fraction for therapeutic applications. A bulk analysis is applied to characterize MSC EVs identity and purity, coupled with the assessment of single EV morphology, size and i...
Article
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Pregnancy is a unique situation of physiological immunomodulation, as well as a strong Multiple Sclerosis (MS) disease modulator whose mechanisms are still unclear. Both maternal (decidua) and fetal (trophoblast) placental cells secrete extracellular vesicles (EVs), which are known to mediate cellular communication and modulate the maternal immune...
Article
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Extracellular vesicles (EVs) have emerged in the last decades as a cell-to-cell communication mechanism. One of their mechanism of action is the direct delivery of their cargo, composed of bioactive molecules to target cells. Different methods (direct electroporation, cell transfection, chemical transfection) were developed to vehicle therapeutic m...
Article
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Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from human obese adipose tissue (AT). Yet, the role of adipocyte-derived EVs in pancreatic β-cells remains to be determined. Here, we explored the effects of EVs, released from both rod...
Article
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At present, there is no reliable biomarker for the diagnosis of traumatic brain injury (TBI). Studies have shown that extracellular vesicles released by damaged cells into biological fluids can be used as potential biomarkers for diagnosis of TBI and evaluation of TBI severity. We hypothesize that the genetic profile of salivary extracellular vesic...
Article
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Acute and chronic renal failure have long been described and now renamed as acute kidney injury (AKI) and chronic kidney disease (CKD). New concepts are emerging in the pathophysiology of kidney diseases. AKI is often caused by triggering factors (e.g., toxic, ischemic, immunologic) either individually or combined such as in sepsis (inflammation an...
Article
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Limitations in the current therapeutic strategies for the prevention of progression of chronic kidney disease (CKD) to end stage renal disease has been a drawback to improving patient recovery. It is therefore imperative that a solution is found to alleviate this problem and improve the health and well-being of patients overall. Aristolochic acid (...
Article
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Extracellular vesicles (EVs) are membrane vesicles released virtually by all cell types. Several studies have shown that stem cell-derived EVs may mimic both in vitro and in vivo the biological effects of the cells. We recently demonstrated that non-alcoholic steatohepatitis (NASH) is inhibited by treatment with human liver stem cells (HLSCs). The...
Article
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Extracellular vesicles (EVs) secreted in biological fluids contain several transcripts of the cell of origin, which may modify the functions and phenotype of proximal and distant cells. Cancer-derived EVs may promote a favorable microenvironment for cancer growth and invasion by acting on stroma and endothelial cells and may favor metastasis format...
Article
The extra-cellular vesicles (EVs) are membrane vesicles carrying proteins, nucleic acids and bioactive lipids of the cell of origin. These vesicles released within the extracellular space and entering into the circulation may transfer to neighboring or distant cells their cargo inducing phenotypical and functional changes that may be relevant in se...
Article
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Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled molecules, miRNAs have a relevant role in the pro-regenerative effects of EVs and are a promisin...
Article
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Background: Neonatal hypoxic ischemic (HI) insult is a leading cause of disability and death in newborns, with therapeutic hypothermia being the only currently available clinical intervention. Thus there is a great need for adjunct and novel treatments for enhanced or alternative post-HI neuroprotection. Extracellular vesicles (EVs) derived from me...
Article
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Extracellular vesicles (EVs) are important mediators of intercellular communication in cancer and in normal tissues. EVs transfer biologically active molecules from the cell of origin to recipient cells. This review summarizes the studies on EVs derived from renal cell carcinoma and from a subpopulation of CD105-positive renal cancer stem cells. Wh...
Article
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A potential therapeutic strategy for diabetes is the transplantation of induced-insulin secreting cells. Based on the common embryonic origin of liver and pancreas, we studied the potential of adult human liver stem-like cells (HLSC) to generate in vitro insulin-producing 3D spheroid structures (HLSC-ILS). HLSC-ILS were generated by a one-step prot...
Article
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Traumatic brain injury (TBI) is a common cause of death and acquired disability in adults and children. Identifying biomarkers for mild TBI (mTBI) that can predict functional impairments on neuropsychiatric and neurocognitive testing after head trauma is yet to be firmly established. Extracellular vesicles (EVs) are known to traffic from the brain...
Chapter
Stem cells act in a paracrine manner through the secretion of biologically active cargo that acts on cells locally and systemically. These active molecules include not only soluble factors but also extracellular vesicles (EVs) that have recently emerged as a mechanism of cell-to-cell communication. EVs act as vehicles that transfer molecules betwee...
Article
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Kaposi's sarcoma (KS) is a malignancy associated to conditions of immune system impairment such as HIV-1 infection and post-transplantation therapy. Here we report that HIV-1-Tat protein, at concentrations well below those detected in AIDS patients, up-regulates the expression of both CD40 and CD154 on KS cells. This occurred also in the presence o...
Article
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With limited therapeutic intervention in preventing the progression to end-stage renal disease, chronic kidney disease (CKD) remains a global health-care burden. Aristolochic acid (AA) induced nephropathy is a model of CKD characterised by inflammation, tubular injury, and interstitial fibrosis. Human liver stem cell-derived extracellular vesicles...
Article
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RNA molecules are essential and fine regulators of important biological processes. Their role is well documented also in the endocrine system, both in physiological and pathological conditions. Increasing interest is arising about the function and the importance of noncoding RNAs shuttled by extracellular vesicles (EVs). In fact, EV membrane protec...
Article
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Serum is an abundant and accessible source of circulating extracellular vesicles (EVs). Serum-EV (sEV) pro-angiogenic capability and mechanisms are herein analyzed using an in vitro assay which predicts sEV angiogenic potential in vivo. Effective sEVs (e-sEVs) also improved vascular remodeling and prevented muscle damage in a mouse model of acute h...
Article
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Background Argininosuccinate synthase (ASS)1 is a urea cycle enzyme that catalyzes the conversion of citrulline and aspartate to argininosuccinate. Mutations in the ASS1 gene cause citrullinemia type I, a rare autosomal recessive disorder characterized by neonatal hyperammonemia, elevated citrulline levels, and early neonatal death. Treatment for t...
Article
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Extra-cellular vesicles (EVs) derived from human bone marrow mesenchymal stromal cells (MSCs) promote the regeneration of kidneys in different animal models of AKI in a manner comparable to the cells of origin. However, due to the heterogeneity observed in the EVs isolated from MSC, it is unclear which population is responsible for the pro-regenera...
Article
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Vesicular-mediated communication between cells appears critical in many biological processes. Extracellular vesicles (EVs) released from healthy and diseased cells are involved in a network of exchange of biologically active molecules. Since EVs present in biological fluids carry the signature of the cell of origin, they are potential biomarkers fo...
Article
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Extracellular vesicles (EVs) that are derived from stem cells are proving to be promising therapeutic options. We herein investigate the therapeutic potential of EVs that have been derived from different stem cell sources, bone-marrow (MSC) and human liver (HLSC), on mesangial cells (MCs) exposed to hyperglycaemia. By expressing a dominant negative...
Article
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Extracellular vesicles (EVs) are considered to be a novel complex mechanism of cell communication within the tumor microenvironment. EVs may act as vehicles for transcription factors and nucleic acids inducing epigenetic changes in recipient cells. Since tumor EVs may be present in patient biological fluids, it is important to investigate their fun...
Article
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Soluble factors and cell-derived extracellular vesicles (EVs) control vascular cell fate during inflammation. The present study investigates the impact of Interleukin 3 (IL-3) on EV release by endothelial cells (ECs), the mechanisms involved in EV release and paracrine actions. We found that IL-3 increases EV release, which is prevented by IL-3Ralp...
Article
Growing evidence suggests that small vesicles actively released from cells may encapsulate transcriptional regulators and RNA molecules. Their ability to interact with neighbouring cells and/or with distant cells through biological fluids, makes them a medium through which intercellular exchange of information can happen. Recently, membrane vesicle...
Article
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Administration of horse amniotic mesenchymal cells (AMCs) and their conditioned medium (AMC-CM) improves the in vivo recovery of spontaneous equine tendon lesions and inhibits in vitro proliferation of peripheral blood mononuclear cells (PBMC). This process may involve microvesicles (MVs) as an integral component of cell-to-cell communication durin...
Article
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Evidence indicates that Alix, an accessory protein of the endosomal sorting complex required for transport (ESCRT), is involved in the biogenesis of extracellular vesicles (EVs). EVs contain selected patterns of microRNAs (miRNAs or miRs); however, little is known about the mechanisms of miRNA enrichment in EVs. The aim of the present study was to...
Article
Administration of horse amniotic mesenchymal cell conditioned medium (AMC-CM) improves the in vivo recovery of spontaneous equine tendon lesions. This effect may involve paracrine mechanisms whose nature remains unknown. It has recently been demonstrated that microvesicles (MV) released from cells are an integral component of cell-to-cell communica...
Article
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Background: Tumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105(+) CSCs) able to release extrac...
Article
Angiogenesis is a tightly regulated process where a number of different players are involved. Recently, a role for membrane vesicles actively released from cells has been proposed. Virtually all cell types may release non-apoptotic membrane vesicles in the nano-size range containing critical components of the cell of origin. The two main categories...
Article
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Prion protein (PrP) is present at extremely low levels in the blood of animals and its detection is complicated by the poor sensitivity of current standard methodologies. Interesting results have been obtained with recent advanced technologies that are able to detect minute amounts of the pathological PrP (PrPSc), but their efficiency is reduced by...
Article
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Growing evidence suggests that transcriptional regulators and secreted RNA molecules encapsulated within membrane vesicles modify the phenotype of target cells. Membrane vesicles, actively released by cells, represent a mechanism of intercellular communication that is conserved evolutionarily and involves the transfer of molecules able to induce ep...
Article
Full-text available
The regenerative mechanisms ascribed to mesenchymal stem cells (MSCs) are classified into 3 categories: differentiating into damaged cell types, supplying nutrients, and improving survival/functions of the endogenous cells via paracrine actions. However, because of the inhospitable microenvironment of the injured tissues, a proportion of the implan...
Article
Mesenchymal stromal cells (MSCs) inhibit natural killer cell proliferation and activity, suppress T lymphocyte proliferation, dendritic cells maturation and B lymphocyte proliferation and activation. Moreover, MSCs may induce regulatory T cells. Several factors released from MSCs have been implicated in their immune-modulatory properties. These inc...
Chapter
The neoformation of blood vessels is a biological process involved in tissue homeostasis and repair as well as in pathologic conditions such as inflammatory diseases and cancer. Endothelial progenitor cells (EPCs) a cell population derived from the bone marrow and circulating in the blood stream, have been shown to take part to these processes. EPC...
Chapter
There is substantial evidence to support the hypothesis that stem cells exert a regenerative effect on damaged tissues/organs by paracrine mechanisms. Stem cells may favor self-tissue/organ repair by means of soluble factor production as well as by release of small vesicles into the extracellular space. Since microvesicles are a heterogeneous popul...
Article
Aims/hypothesis: Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodulatory effect on T cell responses against GAD (g...
Article
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MicroRNAs (miRNAs), a class of small non-protein-encoding RNAs, regulate gene expression via suppression of target mRNAs. MiRNAs are present in body fluids in a remarkable stable form as packaged in microvesicles of endocytic origin, named exosomes. In the present study, we have assessed miRNA expression in urinary exosomes from type 1 diabetic pat...
Patent
Full-text available
The 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 end...
Article
The 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) release...
Article
Full-text available
The concept that extracellular vesicles may act as paracrine/endocrine effectors is based on the evidence that they are able to transport bioactive molecules between cells, either within a defined microenvironment or remotely, by entering the biologic fluids. Extracellular vesicles, including exosomes and microvesicles, may deliver lipids and vario...
Article
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Mesenchymal stem cells (MSCs) have opposite effects on tumor growth, being able either to favour angiogenesis and tumor initiation or to inhibit progression of established tumors. Factors produced by MSCs within the tumor microenvironment may be relevant for their biological effects. Recent studies demonstrated that microvesicles (MVs) are an integ...
Article
Full-text available
Microvesicles (MVs) play a pivotal role in cell-to-cell communication. Recent studies demonstrated that MVs may transfer genetic information between cells. Here, we show that MVs derived from human adult liver stem cells (HLSC) may reprogram in vitro HepG2 hepatoma and primary hepatocellular carcinoma cells by inhibiting their growth and survival....
Article
Numerous preclinical and clinical studies suggest that mesenchymal stem cells, also known as multipotent mesenchymal stromal cells (MSCs), may improve pathologic conditions involving different organs. These beneficial effects initially were ascribed to the differentiation of MSCs into organ parenchymal cells. However, at least in the kidney, this i...
Article
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Several studies have demonstrated that mesenchymal stem cells have the capacity to reverse acute and chronic kidney injury in different experimental models by paracrine mechanisms. This paracrine action may be accounted for, at least in part, by microvesicles (MVs) released from mesenchymal stem cells, resulting in a horizontal transfer of mRNA, mi...