scholarly journals Application of Stem Cell-Derived Extracellular Vesicles as an Innovative Theranostics in Microbial Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Hani Keshavarz Alikhani ◽  
Bahare Shokoohian ◽  
Sama Rezasoltani ◽  
Nikoo Hossein-khannazer ◽  
Abbas Yadegar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Infectious Diseases ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
The Other ◽  
Microbial Pathogens ◽  
Microbial Diseases ◽  
Clinical Complications ◽  
Set Up ◽  
Novel Therapeutic Strategies

Extracellular vesicles (EVs), as nano-/micro-scale vehicles, are membranous particles containing various cargoes including peptides, proteins, different types of RNAs and other nucleic acids, and lipids. These vesicles are produced by all cell types, in which stem cells are a potent source for them. Stem cell-derived EVs could be promising platforms for treatment of infectious diseases and early diagnosis. Infectious diseases are responsible for more than 11 million deaths annually. Highly transmissible nature of some microbes, such as newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), drives researcher’s interest to set up different strategies to develop novel therapeutic strategies. Recently, EVs-based diagnostic and therapeutic approaches have been launched and gaining momentum very fast. The efficiency of stem cell-derived EVs on treatment of clinical complications of different viruses and bacteria, such as SARS-CoV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Staphylococcus aureus, Escherichia coli has been demonstrated. On the other hand, microbial pathogens are able to incorporate their components into their EVs. The microbe-derived EVs have different physiological and pathological impacts on the other organisms. In this review, we briefly discussed biogenesis and the fate of EVs. Then, EV-based therapy was described and recent developments in understanding the potential application of stem cell-derived EVs on pathogenic microorganisms were recapitulated. Furthermore, the mechanisms by which EVs were exploited to fight against infectious diseases were highlighted. Finally, the deriver challenges in translation of stem cell-derived EVs into the clinical arena were explored.

scholarly journals Human Heart Explant-Derived Extracellular Vesicles: Characterization and Effects on the In Vitro Recellularization of Decellularized Heart Valves

2019 ◽  
Vol 20 (6) ◽  
pp. 1279 ◽  
Author(s):  
Amanda Leitolis ◽  
Paula Suss ◽  
João Roderjan ◽  
Addeli Angulski ◽  
Francisco da Costa ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Human Heart ◽  
Heart Valves ◽  
Enrichment Analysis ◽  
Cell Types

Extracellular vesicles (EVs) are particles released from different cell types and represent key components of paracrine secretion. Accumulating evidence supports the beneficial effects of EVs for tissue regeneration. In this study, discarded human heart tissues were used to isolate human heart-derived extracellular vesicles (hH-EVs). We used nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) to physically characterize hH-EVs and mass spectrometry (MS) to profile the protein content in these particles. The MS analysis identified a total of 1248 proteins. Gene ontology (GO) enrichment analysis in hH-EVs revealed the proteins involved in processes, such as the regulation of cell death and response to wounding. The potential of hH-EVs to induce proliferation, adhesion, angiogenesis and wound healing was investigated in vitro. Our findings demonstrate that hH-EVs have the potential to induce proliferation and angiogenesis in endothelial cells, improve wound healing and reduce mesenchymal stem-cell adhesion. Last, we showed that hH-EVs were able to significantly promote mesenchymal stem-cell recellularization of decellularized porcine heart valve leaflets. Altogether our data confirmed that hH-EVs modulate cellular processes, shedding light on the potential of these particles for tissue regeneration and for scaffold recellularization.

scholarly journals Stem Cell-Derived Extracellular Vesicles for Treating Joint Injury and Osteoarthritis

Nanomaterials ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 261 ◽  
Author(s):  
Jiao Li ◽  
Elham Hosseini-Beheshti ◽  
Georges Grau ◽  
Hala Zreiqat ◽  
Christopher Little
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Joint Injury ◽  
Direct Cell ◽  
Almost All ◽  
New Treatments

Extracellular vesicles (EVs) are nanoscale particles secreted by almost all cell types to facilitate intercellular communication. Stem cell-derived EVs theoretically have the same biological functions as stem cells, but offer the advantages of small size, low immunogenicity, and removal of issues such as low cell survival and unpredictable long-term behaviour associated with direct cell transplantation. They have been an area of intense interest in regenerative medicine, due to the potential to harness their anti-inflammatory and pro-regenerative effects to induce healing in a wide variety of tissues. However, the potential of using stem cell-derived EVs for treating joint injury and osteoarthritis has not yet been extensively explored. The pathogenesis of osteoarthritis, with or without prior joint injury, is not well understood, and there is a longstanding unmet clinical need to develop new treatments that provide a therapeutic effect in preventing or stopping joint degeneration, rather than merely relieving the symptoms of the disease. This review summarises the current evidence relating to stem cell-derived EVs in joint injury and osteoarthritis, providing a concise discussion of their characteristics, advantages, therapeutic effects, limitations and outlook in this exciting new area.

scholarly journals Multifaced Roles of the Urokinase System in the Regulation of Stem Cell Niches

Acta Naturae ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 19-32 ◽  
Author(s):  
K. V. Dergilev ◽  
V. V. Stepanova ◽  
I. B. Beloglazova ◽  
Z. I. Tsokolayeva ◽  
E. V. Parfenova
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Biologically Active ◽  
Tissue Cell ◽  
Direct Cell ◽  
Urokinase System ◽  
And Migration ◽  
Stem Cell Niches

Proliferation, subsequent migration to the damaged area, differentiation into appropriate cell types, and/or secretion of biologically active molecules and extracellular vesicles are important processes that underlie the involvement of stem/progenitor cells in the repair and regeneration of tissues and organs. All these functions are regulated through the interaction between stem cells and the microenvironment in the tissue cell niches that control these processes through direct cell-cell interactions, production of the extracellular matrix, release of extracellular vesicles, and secretion of growth factors, cytokines, chemokines, and proteases. One of the most important proteolytic systems involved in the regulation of cell migration and proliferation is the urokinase system represented by the urokinase plasminogen activator (uPA, urokinase), its receptor (uPAR), and inhibitors. This review addresses the issues of urokinase system involvement in the regulation of stem cell niches in various tissues and analyzes the possible effects of this system on the signaling pathways responsible for the proliferation, programmed cell death, phenotype modulation, and migration properties of stem cells.

scholarly journals Microbial extracellular RNAs and their roles in human diseases

2020 ◽  
Vol 245 (10) ◽  
pp. 845-850 ◽  
Author(s):  
Heon-Jin Lee
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Human Cells ◽  
The Body ◽  
Human Diseases ◽  
Host Responses ◽  
Target Cells ◽  
Extracellular Rna ◽  
Communication Signals ◽  
Novel Therapeutic Strategies

Extracellular RNAs (exRNAs) are released by extracellular vesicles, small membranous nanoparticles secreted by all cell types. When transported into cells, exRNAs can modulate gene expression or cellular responses in the target cells since many small RNAs have regulatory functions. Indeed, it is widely acknowledged that endogenous exRNAs in the human body are related to various diseases. However, microbial exRNAs have been less studied, and their connection to host diseases has just begun to be explored. In this review, I will discuss analytical methods for exRNAs and the potential use of exRNAs as disease biomarkers. I also consider current progress in understanding the regulation of host mechanisms by microbial exRNAs as inter-kingdom communication, efforts to utilize extracellular vesicles as therapeutic vehicles loaded with engineered RNA cargos, and a putative connection between microbial exRNA-based regulation of host responses and human diseases such as Alzheimer’s. This overview aims to present novel insights into pathogenesis with regard to the function of microbial exRNAs as “disease-relevant travelers.” Impact statement The number of commensal bacteria in the body surpasses the number of actual human cells. Thus, various interactions between microbes and human cells constitute an inevitable phenomenon. Recent evidence has led to bacterial extracellular RNAs (exRNAs) being proposed as good candidates for microbe–host inter-kingdom communication tools as they can modulate the expression of host genes. However, research findings on the relevance of interactions between extracellular RNA and human diseases are still in their infancy. Nevertheless, substantial data suggest that microbial exRNAs are implicated in various human diseases both at local and distant sites. By exploring various scenarios for the involvement of microbial exRNAs in human diseases, we may better understand the role of exRNAs as “communication signals” for diseases and thereby develop novel therapeutic strategies by using them and their carrier extracellular vesicles.

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

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 359
Author(s):  
Maria Chiara Ciferri ◽  
Rodolfo Quarto ◽  
Roberta Tasso
Keyword(s):  
Clinical Trials ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Types ◽  
Storage Conditions ◽  
Clinical Applications ◽  
The Other ◽  
The Past ◽  
Therapeutic Tools ◽  
And Storage

Extracellular vesicles (EVs) are ubiquitous masters of intercellular communication, being detectable in tissues, circulation, and body fluids. Their complex cargo reflects the (patho)physiologic status of the cells from which they originate. Due to these properties, the potential of EVs, and in particular exosomes, to serve as biomarkers or therapeutics has grown exponentially over the past decade. On one side, numerous studies have demonstrated that EV-associated nucleic acids and proteins are implicated in cancer progression, as well as neurodegenerative, infectious, and autoimmune disorders. On the other, the therapeutic use of EVs secreted by various cell types, and in particular stem/progenitor cells, present significant advantages in comparison to the corresponding parental cells, such as the less complex production and storage conditions. In this review, we examine some of the major pre-clinical studies dealing with EVs and exosomes, that led to the development of numerous completed clinical trials.

scholarly journals Stem Cell Transplantation in Cardiovascular Disease: An Update

2012 ◽  
Vol 40 (3) ◽  
pp. 833-838 ◽  
Author(s):  
M Teng ◽  
Z Geng ◽  
L Huang ◽  
X Zhao
Keyword(s):  
Stem Cell ◽  
Cardiovascular Diseases ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Phase 1 ◽  
Cell Types ◽  
Therapeutic Strategies ◽  
Routes Of Administration ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Despite the development of novel therapeutic strategies, cardiovascular diseases remain the main cause of morbidity and mortality worldwide. Many phase 1 and 2 clinical trials have reported the safety, feasibility and promising potential of stem cell transplantation, however, the optimal cell types, timing of infusion, cell dosage and routes of administration remain to be determined. This paper reviews the findings of various clinical studies and discusses the challenges facing the delivery of stem cell therapy in cardiovascular diseases.

scholarly journals BMSC-derived extracellular vesicles intervened the pathogenic changes of scleroderma in mice through miRNAs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiahui Jin ◽  
Qingjian Ou ◽  
Zhe Wang ◽  
Haibin Tian ◽  
Jing-Ying Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Western Blot ◽  
Signaling Pathways ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Similar Efficacy ◽  
Mrna Levels ◽  
Mirna Sequencing

Abstract Background Systemic sclerosis (SSc) is a disease that features severe fibrosis of the skin and lacks effective therapy. Bone marrow mesenchymal stem cell (BMSC)-derived extracellular vesicles (EVs) are potential stem cell-based tools for the treatment of SSc. Methods BMSCs were isolated from the bone marrow of mice and identified with surface markers according to multilineage differentiation. EVs were isolated from the BMSC culture medium by ultracentrifugation and identified with a Nanosight NS300 particle size analyzer, transmission electron microscopy (TEM), and western blot. The microRNAs (miRNAs) of BMSC-derived EVs (BMSC-EVs) were studied via miRNA sequencing (miRNA-seq) and bioinformatic analysis. An SSc mouse model was established via subcutaneous bleomycin (BLM) injection, and the mice were treated with BMSCs or BMSC-derived EVs. Skin tissues were dissociated and analyzed with H&E staining, RNA sequencing (RNA-seq), western blot, and immunohistochemical staining. Results Evident pathological changes, like fibrosis and inflammation, were induced in the skin of BLM-treated mice. BMSCs and BMSC-EVs effectively intervened such pathological manifestations and disease processes in a very similar way. The effects of the BMSC-EVs were found to be caused by the miRNAs they carried, which were proven to be involved in regulating the proliferation and differentiation of multiple cell types and in multiple EV-related biological processes. Furthermore, TGF-β1-positive cells and α-SMA-positive myofibroblasts were significantly increased in the scleroderma skin of BLM-treated mice but evidently reduced in the scleroderma skin of the EV-treated SSc group. In addition, the numbers of mast cells and infiltrating macrophages and lymphocytes were evidently increased in the skin of BLM-treated mice but significantly reduced by EV treatment. In line with these observations, there were significantly higher mRNA levels of the inflammatory cytokines Il6, Il10, and Tnf-α in SSc mice than in control mice, but the levels decreased following EV treatment. Through bioinformatics analysis, the TGFβ and WNT signaling pathways were revealed to be closely involved in the pathogenic changes seen in mouse SSc, and these pathways could be therapeutic targets for treating the disease. Conclusions BMSC-derived EVs could be developed as a potential therapy for treating skin dysfunction in SSc, especially considering that they show similar efficacy to BMSCs but have fewer developmental regulatory requirements than cell therapy. The effects of EVs are generated by the miRNAs they carry, which alleviate SSc pathogenic changes by regulating the WNT and TGFβ signaling pathways.

scholarly journals The mini player with diverse functions: extracellular vesicles in cell biology, disease, and therapeutics

2021 ◽  
Author(s):  
Abhimanyu Thakur ◽  
Xiaoshan Ke ◽  
Ya-Wen Chen ◽  
Pedram Motallebnejad ◽  
Kui Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Biology ◽  
Cancer Biology ◽  
Cell Types ◽  
Research Progress ◽  
Drug Delivery Vehicles ◽  
Significant Research

AbstractExtracellular vesicles (EVs) are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids. The classification of EVs includes exosomes, microvesicles, and apoptotic bodies, dependent on various factors such as size, markers, and biogenesis pathways. The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways. EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication, contributing to organ development and the progression of cancer. This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche, and cellular communication among different germ layers in developmental biology. In addition, it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles. All such discoveries have been facilitated by tremendous technological advancements in EV-associated research, especially the microfluidics systems. Their pros and cons in the context of characterization of EVs are also extensively discussed in this review. This review also deliberates the role of EVs in normal cell processes and disease conditions, and their application as a diagnostic and therapeutic tool. Finally, we propose future perspectives for EV-related research in stem cell and cancer biology.

scholarly journals Coincubation as miR-Loading Strategy to Improve the Anti-Tumor Effect of Stem Cell-Derived EVs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 76
Author(s):  
Alessia Brossa ◽  
Marta Tapparo ◽  
Valentina Fonsato ◽  
Elli Papadimitriou ◽  
Michela Delena ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Cell Invasion ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Target Cells ◽  
Therapeutic Tool ◽  
Rnase Digestion ◽  
Set Up

Extracellular vesicles are considered a novel therapeutic tool, due to their ability to transfer their cargoes to target cells. Different strategies to directly load extracellular vesicles with RNA species have been proposed. Electroporation has been used for the loading of non-active vesicles; however, the engineering of vesicles already carrying a therapeutically active cargo is still under investigation. Here, we set up a coincubation method to increase the anti-tumor effect of extracellular vesicles isolated from human liver stem cells (HLSC-EVs). Using the coincubation protocol, vesicles were loaded with the anti-tumor miRNA-145, and their effect was evaluated on renal cancer stem cell invasion. Loaded HLSC-EVs maintained their integrity and miR transfer ability. Loaded miR-145, but not miR-145 alone, was protected by RNAse digestion, possibly due to its binding to RNA-binding proteins on HLSC-EV surface, such as Annexin A2. Moreover, miR-145 coincubated HLSC-EVs were more effective in inhibiting the invasive properties of cancer stem cells, in comparison to naïve vesicles. The protocol reported here exploits a well described property of extracellular vesicles to bind nucleic acids on their surface and protect them from degradation, in order to obtain an effective miRNA loading, thus increasing the activity of therapeutically active naïve extracellular vesicles.

scholarly journals Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 957
Author(s):  
Cristina Mas-Bargues ◽  
Jorge Sanz-Ros ◽  
Aurora Román-Domínguez ◽  
Lucia Gimeno-Mallench ◽  
Marta Inglés ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Cell Function ◽  
Cell Types ◽  
Culture Conditions ◽  
Target Cells ◽  
Activity Levels ◽  
Functional Changes

Aging is accompanied by the accumulation of senescent cells that alter intercellular communication, thereby impairing tissue homeostasis and reducing organ regenerative potential. Recently, the administration of mesenchymal stem cells (MSC)-derived extracellular vesicles has proven to be more effective and less challenging than current stem cell-based therapies. Extracellular vesicles (EVs) contain a cell-specific cargo of proteins, lipids and nucleic acids that are released and taken up by probably all cell types, thereby inducing functional changes via the horizontal transfer of their cargo. Here, we describe the beneficial properties of extracellular vesicles derived from non-senescent MSC, cultured in a low physiological oxygen tension (3%) microenvironment into prematurely senescent MSC, cultured in a hyperoxic ambient (usual oxygen culture conditions, i.e., 21%). We observed that senescent MCS, treated with EVs from non-senescent MCS, showed reduced SA-β-galactosidase activity levels and pluripotency factor (OCT4, SOX2, KLF4 and cMYC, or OSKM) overexpression and increased glycolysis, as well as reduced oxidative phosphorylation (OXPHOS). Moreover, these EVs’ cargo induced the upregulation of miR-302b and HIF-1α levels in the target cells. We propose that miR-302b triggered HIF-1α upregulation, which in turn activated different pathways to delay premature senescence, improve stemness and switch energetic metabolism towards glycolysis. Taken together, we suggest that EVs could be a powerful tool to restore altered intercellular communication and improve stem cell function and stemness, thus delaying stem cell exhaustion in aging.

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