• cell therapy
• exosome
• extracellular vesicle
• cell engineering
• stem cell
• immunotherapy
• drug delivery

• Natural Science Foundation of Nantong Municipality
• Xi’an Jiaotong-Liverpool University
• Natural Science Foundation of Jiangsu Province

• COVID‐19
• biomimetic vesicles
• cytokine storm
• extracellular vesicles
• neutralize viruses

• Humans
• Biomimetic Materials/chemistry
• Biomimetic Materials/therapeutic use
• COVID-19/therapy
• COVID-19/virology
• COVID-19 Drug Treatment
• Cytokines/metabolism
• Extracellular Vesicles/metabolism
• SARS-CoV-2/physiology

• 82002253 National Natural Science Foundation of China
• 2023A03J0521 Guangzhou Key Laboratory of Clinical and Basic Research in Otolaryngology
• 2019GX08 Guangzhou Clinical High Tech Project
• 2023C-GX05 Guangzhou Clinical High Tech Project
• 2024CL-GX07 Guangzhou Clinical High Tech Project

• biomedical application
• clinical treatment
• delivery strategy
• extracellular vesicles
• plant

• National Natural Science Foundation of China

• engineering strategies
• mesenchymal stem cell extracellular vesicles
• solid tumors
• tissue regeneration
• tumor treatment

• Humans
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/transplantation
• Mesenchymal Stem Cells/metabolism
• Neoplasms/therapy
• Animals
• Tumor Microenvironment

• cancer
• drug delivery
• nanoparticle design
• nanotheranostics
• treatment

• Humans
• Nanostructures/chemistry
• Nanostructures/therapeutic use
• Neoplasms/therapy
• Neoplasms/drug therapy
• Drug Delivery Systems
• Head and Neck Neoplasms/therapy
• Head and Neck Neoplasms/drug therapy
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/administration & dosage
• Nanoparticles/chemistry
• Nanoparticles/therapeutic use
• Animals

• Brigitte and Dr. Konstanze Wegener Stiftung Brigitte and Dr. Konstanze Wegener Stiftung

• angiogenesis
• cancer
• lncRNA
• mechanism
• multidimensional modification
• therapeutic application

• RNA, Long Noncoding/genetics
• Humans
• Neovascularization, Pathologic/genetics
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/therapy
• Neoplasms/blood supply
• Gene Expression Regulation, Neoplastic
• Animals
• Angiogenesis Inhibitors/therapeutic use
• Molecular Targeted Therapy
• Angiogenesis

• National Natural Science Foundation of China
• Natural Science Foundation of Shandong Province
• China Postdoctoral Science Foundation

• EBV-related fevers
• Epstein-Barr
• biomarker.
• microRNAs
• therapeutic targets
• virus

• Humans
• MicroRNAs/genetics
• Herpesvirus 4, Human/genetics
• Epstein-Barr Virus Infections/complications
• Epstein-Barr Virus Infections/genetics
• Epstein-Barr Virus Infections/diagnosis
• Infectious Mononucleosis
• Biomarkers

• 81904072 National Natural Science Foundation of China
• 2018YFC1704102 Ministry of Science and Technology of China
• A1-W20-205-01-0402-18 Training Program of Xing-lin Heritage-type Talents in Shanghai University of Traditional Chinese Medicine
• A1-GY20-101-0101 Climbing and Trekking Talent Training Program in Basic Medical College, Shanghai University of Traditional Chinese Medicine

• Biogenesis
• Biological barriers
• Cancer
• Drug delivery
• Exosome
• Extracellular vesicle
• Isolation

• Exosomes/metabolism
• Tissue Distribution
• Drug Delivery Systems/methods
• MicroRNAs/metabolism
• Proteins/metabolism
• RNA, Small Interfering/metabolism
• Nucleic Acids
• Neoplasms/drug therapy
• Neoplasms/metabolism

• DNA tetrahedra
• cell imaging
• dynamic assembly
• gene therapy
• in-situ delivery
• miRNA

• CRISPR/Cas systems
• Cancer therapy
• Exosome
• Vexosome
• Viral vectors

• Biogenesis
• Clinical trial
• Drug loading
• Exosomes
• Extracellular vesicles
• Proteins
• RNA
• Surface modification

• Carrier
• Interferon
• Oncogenes
• Oncolytic virus
• Oncovirus
• Vehicle

• Exosome
• biogenesis
• extracellular vesicles
• manipulation
• therapeutics

• Bone marrow mesenchymal stem cell
• Bone regeneration
• Exosome
• Extracellular vesicle
• Micro-RNA
• Osteogenesis

Flaviviruses are a spectrum of vector-borne RNA viruses that cause potentially severe diseases in humans including encephalitis, acute-flaccid paralysis, cognitive disorders and foetal abnormalities. Japanese encephalitis virus (JEV), Zika virus (ZIKV), West Nile virus (WNV) and Dengue virus (DENV) are globally emerging pathogens that lead to epidemics and outbreaks with continued transmission to newer geographical areas over time. In the past decade, studies have focussed on understanding the pathogenic mechanisms of these viruses in a bid to alleviate their disease burden. MicroRNAs (miRNAs) are short single-stranded RNAs that have emerged as master-regulators of cellular gene expression. The dynamics of miRNAs within a cell have the capacity to modulate hundreds of genes and, consequently, their physiological manifestation. Increasing evidence suggests their role in host response to disease and infection including cell survival, intracellular viral replication and immune activation. In this review, we aim to comprehensively update published evidence on the role of miRNAs in host cells infected with the common neurotropic flaviviruses, with an increased focus on neuropathogenic mechanisms. In addition, we briefly cover therapeutic advancements made in the context of miRNA-based antiviral strategies.

siRNA interference, commonly referred to as gene silence, is a biological mechanism that inhibits gene expression in disorders such as cancer. It may enhance the precision, efficacy, and stability of medicines, especially genetic therapies to some extent. However, obstacles such as the delivery of oligonucleotide drugs to inaccessible areas of the body and the prevalence of severe side effects must be overcome. To maximize their potential, it is thus essential to optimize their distribution to target locations and limit their toxicity to healthy cells. The action of siRNA may be harnessed to delete a similar segment of mRNA that encodes a protein that causes sickness. The absence of an efficient delivery mechanism that shields siRNA from nuclease degradation, delivers it to cancer cells and releases it into the cytoplasm of specific cancer cells without causing side effects is currently the greatest obstacle to the practical implementation of siRNA therapy. This article focuses on combinations of siRNA with chemotherapeutic drug delivery systems for the treatment of cancer and gives an overview of several nanocarrier formulations in both research and clinical applications.

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive dementia. Accumulation of β–amyloid peptide 1–42 and phosphorylation of tau protein in the brain are the two main pathological features of AD. However, comprehensive studies have shown that neuroinflammation also plays a crucial role in the pathogenesis of AD. Neuroinflammation is associated with neuronal death and abnormal protein aggregation and promotes the pathological process of β-amyloid peptide 1–42 and tau protein. The inflammatory components associated with AD include glial cells, complement system, cytokines and chemokines. In recent years, some researchers have focused on exosomes, a type of membrane nano vesicles. Exosomes can transport proteins, lipids, microRNAs and other signaling molecules to participate in a variety of signaling pathways for signal transmission or immune response, affecting the activity of target cells and participating in important pathophysiological processes. Therefore, exosomes play an essential role in intercellular communication and may mediate neuroinflammation to promote the development of AD. This paper reviews the occurrence and development of neuroinflammation and exosomes in AD, providing a deeper understanding of the pathogenesis of AD. Furthermore, the role of exosomes in the pathogenesis and treatment of AD is further described, demonstrating their potential as therapeutic targets for neuroinflammation and AD in the future.

• angiogenesis
• cancer
• diagnostic tools
• exosomes
• extracellular vesicles
• immune response
• long non-coding RNAs
• metastasis
• miRNA

• Extracellular Vesicles/metabolism
• Humans
• MicroRNAs/genetics
• Neoplasms/drug therapy
• Neoplasms/therapy
• RNA, Long Noncoding/metabolism
• Tumor Microenvironment
• Vaccines

• IFP-2020-28 DSR Deanship of Scientific Research, Majmaah University, Saudi Arabia

• epigenetic regulation
• flavivirus
• host-response
• micrornas
• neurotropism

• Antiviral Agents
• Flavivirus/genetics
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Virus Replication/genetics
• Zika Virus/genetics
• Zika Virus/metabolism
• Zika Virus Infection

The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape lysosomal destruction. Most artificial nanocarriers suffer from intrinsic limitations that prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and is usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and EVs. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with a higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into EVs.

• RNA sorting
• extracellular vesicles
• fusion protein
• target delivery

• biomarker
• diagnosis
• exosome
• lung cancer
• tumor-derived exosome

Background: MicroRNA (abbreviated miRNA)-based treatment holds great promise for application as clinical antitumor therapy, but good carriers for delivery of the miRNA drug are lacking. Exosomes secreted by mesenchymal stem cells (MSCs) have proved to be safe, and exogenously modified exosomes may potentially represent an excellent drug delivery vehicle.

Methods: In this study, we designed a delivery nano system using single-stranded variable fragment (scFv)-modified exosomes derived from human cord blood MSCs. Genetic engineering technology was used to obtain anti-Glypican 3 (GPC3) scFv-modified exosomes, which were then loaded with miR-26a mimics through electroporation.

Results: Results of electron microscopy and dynamic light scattering indicated that the diameter of the drug-carrying exosomes was about 160 nm. Furthermore, anti-GPC3 scFv-modified exosomes effectively delivered miR-26a to GPC3-positive hepatocellular carcinoma cells, thereby inhibiting cell proliferation and migration by regulating the expression of downstream target genes of miR-26a. The exosomes-based nano system displayed favorable anti-tumor effect in vivo with no obvious side effects.

Conclusion: Our data provided a new perspective for the use of exosome delivery systems for miRNA-based antitumor therapy.

• Glypican 3
• drug delivery
• exosomes
• miR-26a
• nanosystem

Extracellular vesicles (EVs) subtype, exosome is an extracellular nano-vesicle that sheds from cells’ surface and originates as intraluminal vesicles during endocytosis. Firstly, it was thought to be a way for the cell to get rid of unwanted materials as it loaded selectively with a variety of cellular molecules, including RNAs, proteins, and lipids. However, it has been found to play a crucial role in several biological processes such as immune modulation, cellular communication, and their role as vehicles to transport biologically active molecules. The latest discoveries have revealed that many viruses export their viral elements within cellular factors using exosomes. Hijacking the exosomal pathway by viruses influences downstream processes such as viral propagation and cellular immunity and modulates the cellular microenvironment. In this manuscript, we reviewed exosomes biogenesis and their role in the immune response to viral infection. In addition, we provided a summary of how some pathogenic viruses hijacked this normal physiological process. Viral components are harbored in exosomes and the role of these exosomes in viral infection is discussed. Understanding the nature of exosomes and their role in viral infections is fundamental for future development for them to be used as a vaccine or as a non-classical therapeutic strategy to control several viral infections.

• extracellular vesicles (EVs)
• immune evasion
• pathogenesis and immune modulation

• Biomimetic vaccine
• Nanoparticles
• Pathogen
• Vaccine delivery

• Delivery vehicles
• Exosomes
• Extracellular vesicles
• Tumor-derived exosomes

• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Cancer Vaccines/chemistry
• Cancer Vaccines/therapeutic use
• Drug Delivery Systems
• Exosomes/chemistry
• Extracellular Vesicles/chemistry
• Genetic Therapy/methods
• Humans
• Neoplasms/therapy
• Translational Science, Biomedical

• Drug delivery
• Exosomes
• Extracellular vesicle surface
• Extracellular vesicles
• Protein delivery
• RNA delivery
• Reporter systems
• Small molecules
• Uptake mechanisms

Several oncolytic viruses applications have been approved in the clinic or in different phases of clinical trials. However, these methods have some rudimentary problems. Therefore, to enhance the delivery and quality of treatment, considering the advantage of cell carrier-based methods such as Mesenchymal Stem Cells (MSC) have been proposed. This study was designed to evaluate the performance and quality of cancer treatment based on MSCs loaded by oncolytic reovirus in the cancerous C57BL/6 mouse model. Also, we evaluated MSCs migration potency in vitro and in vivo following the oncolytic reovirus infection.

C57BL/6 mice were inoculated with TC-1 cell lines and tumors were established in the right flank. Mice were systemically treated with reovirus, MSCs-loaded with reovirus, MSCs, and PBS as a control in separated groups. Effects of infected AD-MSCs with reovirus on tumor growth and penetration in the tumor site were monitored. All groups of mice were monitored for two months in order to therapeutic and anticancer potential. After treatments, tumor size alteration and apoptosis rate, as well as cytokine release pattern was assessed.

The results of the current study indicated that the effect of reovirus infection on AD-MSCs is not devastating the migration capacity especially in MOI 1 and 5 while intact cells remain. On the other hand, MSCs play an efficient role as a carrier to deliver oncolytic virus into the tumor site in comparison with systemic administration of reovirus alone. Apoptosis intensity relies on viral titration and passing time. Followed by systemic administration, treatment with oncolytic reovirus-infected AD-MSCs and MSCs alone had shown significant inhibition in tumor growth. Also, treatment by reovirus causes an increase in IFN-γ secretion.

The results of in vitro and in vivo study confirmed the tumor-homing properties of infected AD-MSCs and the significant antitumor activity of this platform. Hence, our results showed that the cell carrier strategy using oncolytic reovirus-loaded AD-MSCs enhanced virus delivery, infiltration, and antitumor activity can be effectively applied in most cancers.

• Anti-tumor effect
• Drug Delivery Systems
• IFN-γ
• MOI
• Targeted therapy
• Virus titer

• Cell survival
• Cell transplantation
• Liver disease
• Mesenchymal stromal cells

Exosomes are natural nanoscale bilayer phospholipid vesicles that can be secreted by almost all types of cells and are detected in almost all types of body fluids. Exosomes are effective mediators of cell–cell signaling communication because of their ability to carry and transfer a variety of bioactive molecules, including non-coding RNAs. Non-coding RNAs have also been found to exert strong effects on a variety of biological processes, including tumorigenesis. Many researchers have established that exosomes encapsulate bioactive non-coding RNAs that alter the biological phenotype of specific target cells in an autocrine or a paracrine manner. However, the mechanism by which the producer cells package non-coding RNAs into exosomes is not well understood. This review focuses on the current research on exosomal non-coding RNAs, including the biogenesis of exosomes, the possible mechanism of sorting non-coding RNAs, their biological functions, and their potential for clinical application in the future.

• cell-cell communication
• exosome
• extracellular vesicles
• ncRNAs
• non-coding RNAs
• sorting mechanism

Malignant tumors have become one of the major causes of human death, but there remains a lack of effective methods for tiny tumor diagnosis, metastasis warning, clinical efficacy prediction, and effective treatment. In this context, localizing tiny tumors via imaging and non-invasively extracting molecular information related to tumor proliferation, invasion, metastasis, and drug resistance from the tumor microenvironment have become the most fundamental tasks faced by cancer researchers. Tumor-associated microenvironmental physiological parameters, such as hypoxia, acidic extracellular pH, protease, reducing conditions, and so forth, have much to do with prognostic indicators for cancer progression, and impact therapeutic administrations. By combining with various novel nanoparticle-based activatable probes, molecular imaging technologies can provide a feasible approach to visualize tumor-associated microenvironment parameters noninvasively and realize accurate treatment of tumors. This review focuses on the recent achievements in the design of “smart” nanomedicine responding to the tumor microenvironment-related features and highlights state-of- the-art technology in tumor imaging diagnosis and therapy.

• microenvironment
• multi-modal probe
• nanomedicine
• target-triggering
• tumor theranostics

• Exosomes
• biosynthesis
• drug delivery
• nanocarrier
• targeted drug delivery

• RNA interference
• cancer
• delivery agents
• exogenous dsRNA
• oligonucleotides

• Gene Silencing
• Humans
• Neoplasms/genetics
• Neoplasms/therapy
• RNA Interference
• RNA, Double-Stranded/genetics
• RNA, Double-Stranded/therapeutic use

• #2019-0546 (FSUS-2020-0040) Ministry of Education and Science of Russian Federation

• Extracellular vesicles
• exosomes
• musculoskeletal regeneration
• optimizing exosomes
• therapeutic application

Although multiple drugs are accessible for recovering liver function in patients, none are considered efficient. Liver transplantation is the mainstay therapy for end-stage liver fibrosis. However, the worldwide shortage of healthy liver donors, organ rejection, complex surgery, and high costs are prompting researchers to develop novel approaches to deal with the overwhelming liver fibrosis cases. Mesenchymal stem cell (MSC) therapy is an emerging alternative method for treating patients with liver fibrosis. However, many aspects of this therapy remain unclear, such as the efficiency compared to conventional treatment, the ideal MSC sources, and the most effective way to use it. Because bone marrow (BM) is the largest source for MSCs, this paper used a systematic review approach to study the therapeutic efficiency of MSCs against liver fibrosis and related factors. We systematically searched multiple published articles to identify studies involving liver fibrosis and BM-MSC-based therapy. Analyzing the selected studies showed that compared with conventional treatment BM-MSC therapy may be more efficient for liver fibrosis in some cases. In contrast, the cotreatment presented a more efficient way. Nevertheless, BM-MSCs are lacking as a therapy for liver fibrosis; thus, this paper also reviews factors that affect BM-MSC efficiency, such as the implementation routes and strategies employed to enhance the potential in alleviating liver fibrosis. Ultimately, our review summarizes the recent advances in the BM-MSC therapy for liver fibrosis. It is grounded in recent developments underlying the efficiency of BM-MSCs as therapy, focusing on the preclinical in vivo experiments, and comparing to other treatments or sources and the strategies used to enhance its potential while mentioning the research gaps.

• Bone marrow
• Mesenchymal stem cells
• Liver fibrosis
• In vivo
• Efficiency

• Animals
• Bone Marrow
• Bone Marrow Cells
• Disease Models, Animal
• Humans
• Liver Cirrhosis/therapy
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells

Extracellular Vesicles (EVs) represent a heterogeneous population of membranous cell-derived structures, including cargo-oriented exosomes and microvesicles. EVs are functionally associated with intercellular communication and play an essential role in multiple physiopathological conditions. Shedding of EVs is frequently increased in malignancies and their content, including proteins and nucleic acids, altered during carcinogenesis and cancer progression. EVs-mediated intercellular communication between tumor cells and between tumor and stromal cells can modulate, through cargo miRNA, the survival, progression, and drug resistance in cancer conditions. These consolidated suggestions and EVs’ stability in bodily fluids have led to extensive investigations on the potential employment of circulating EVs-derived miRNAs as tumor biomarkers and potential therapeutic vehicles. In this review, we highlight the current knowledge about circulating EVs-miRNAs in human cancer and the application limits of these tools, discussing their clinical utility and challenges in functions such as in biomarkers and instruments for diagnosis, prognosis, and therapy.

• biomarkers
• cancer
• clinical studies
• diagnosis
• exosomes
• extracellular vesicles
• microRNA
• microvesicles
• nucleic acids cargo
• therapy

• Biomarkers, Tumor/metabolism
• Cell Communication/genetics
• Cell-Derived Microparticles/metabolism
• Disease Progression
• Exosomes/metabolism
• Extracellular Vesicles/genetics
• Extracellular Vesicles/metabolism
• Humans
• MicroRNAs/genetics
• MicroRNAs/pharmacology
• Neoplasms/pathology
• Prognosis
• Tumor Microenvironment/genetics

MicroRNAs (miRNAs) are small noncoding RNAs that function at the posttranscriptional level in the cellular regulation process. miRNA expression exerts vital effects on cell growth such as cell proliferation and survival. In cancers, miRNAs have been shown to initiate carcinogenesis, where overexpression of oncogenic miRNAs (oncomiRs) or reduced expression of tumor suppressor miRNAs has been reported. In this review, we discuss the involvement of miRNAs in tumorigenesis, the role of synthetic miRNAs as either mimics or antagomirs to overcome cancer growth, miRNA delivery, and approaches to enhance their therapeutic potentials.

• Fundación Científica Asociación Española Contra el Cáncer
• H2020 European Research Council
• Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina
• Instituto de Salud Carlos III
• European Regional Development Fund

• NANPs
• RNA nanotechnology
• SELEX
• aptamers
• exosomes
• immunotherapy
• nucleic acid delivery
• therapeutic nucleic acids

• Animals
• Aptamers, Nucleotide
• Cell Line, Tumor
• Drug Delivery Systems
• Humans
• Immunotherapy
• Mice
• Nanomedicine/methods
• Nanoparticles/chemistry
• Nanoparticles/therapeutic use
• Neoplasms/therapy
• Nucleic Acids/chemistry
• Nucleic Acids/therapeutic use
• SELEX Aptamer Technique/methods

• R01 GM120487 NIGMS NIH HHS

Adipose stem cells (ASCs) are a crucial element in bone tissue engineering (BTE). They are easy to harvest and isolate, and they are available in significative quantities, thus offering a feasible and valid alternative to other sources of mesenchymal stem cells (MSCs), like bone marrow. Together with an advantageous proliferative and differentiative profile, they also offer a high paracrine activity through the secretion of several bioactive molecules (such as growth factors and miRNAs) via a sustained exosomal release which can exert efficient conditioning on the surrounding microenvironment. BTE relies on three key elements: (1) scaffold, (2) osteoprogenitor cells, and (3) bioactive factors. These elements have been thoroughly investigated over the years. The use of ASCs has offered significative new advancements in the efficacy of each of these elements. Notably, the phenotypic study of ASCs allowed discovering cell subpopulations, which have enhanced osteogenic and vasculogenic capacity. ASCs favored a better vascularization and integration of the scaffolds, while improvements in scaffolds' materials and design tried to exploit the osteogenic features of ASCs, thus reducing the need for external bioactive factors. At the same time, ASCs proved to be an incredible source of bioactive, proosteogenic factors that are released through their abundant exosome secretion. ASC exosomes can exert significant paracrine effects in the surroundings, even in the absence of the primary cells. These paracrine signals recruit progenitor cells from the host tissues and enhance regeneration. In this review, we will focus on the recent discoveries which have involved the use of ASCs in BTE. In particular, we are going to analyze the different ASCs' subpopulations, the interaction between ASCs and scaffolds, and the bioactive factors which are secreted by ASCs or can induce their osteogenic commitment. All these advancements are ultimately intended for a faster translational and clinical application of BTE.

Dynamic and adaptive self-assembly systems are able to sense an external or internal (energy or matter) input and respond via chemical or physical property changes. Nanomaterials that show such transient behavior have received increasing interest in the field of nanomedicine due to improved spatiotemporal control of the nanocarrier function. In this regard, much can be learned from the field of systems chemistry and bottom-up synthetic biology, in which complex and intelligent networks of nanomaterials are designed that show transient behavior and function to advance our understanding of the complexity of living systems. In this Perspective, we highlight the recent advancements in adaptive nanomaterials used for nanomedicine and trends in transient responsive self-assembly systems to envisage how these fields can be integrated for the formation of next-generation adaptive stimuli-responsive nanocarriers in nanomedicine.

• angiogenesis
• anti-inflammatory agents
• extracellular vesicles
• microRNA
• secretome

• Adipose Tissue/cytology
• Adipose Tissue/metabolism
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Human Umbilical Vein Endothelial Cells/cytology
• Human Umbilical Vein Endothelial Cells/metabolism
• Humans
• Interleukin-1beta/genetics
• Interleukin-1beta/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neovascularization, Physiologic
• Stem Cells/cytology
• Stem Cells/metabolism
• Wound Healing

• P20 GM103638 NIGMS NIH HHS
• T32 GM008359 NIGMS NIH HHS

Human adipose-derived stem cells (ADSCs) can release exosomes; however, their specific functions remain elusive. In this study, we verified that exosomes derived from osteogenically differentiated ADSCs can promote osteogenic differentiation of ADSCs. Furthermore, in order to investigate the importance of exosomal microRNAs (miRNAs) in osteogenic differentiation of ADSCs, we used microarray assays to analyze the expression profiles of exosomal miRNAs derived from undifferentiated as well as osteogenically differentiated ADSCs; 201 miRNAs were upregulated and 33 miRNAs were downregulated between the two types of exosomes. Additionally, bioinformatic analyses, which included gene ontology analyses, pathway analysis, and miRNA-mRNA-network investigations, were performed. The results of these analyses revealed that the differentially expressed exosomal miRNAs participate in multiple biological processes, such as gene expression, synthesis of biomolecules, cell development, differentiation, and signal transduction, among others. Moreover, we found that these differentially expressed exosomal miRNAs connect osteogenic differentiation to processes such as axon guidance, MAPK signaling, and Wnt signaling. To the best of our knowledge, this is the first study to identify and characterize exosomal miRNAs derived from osteogenically differentiated ADSCs. This study confirms that alterations in the expression of exosomal miRNAs can promote osteogenic differentiation of ADSCs, which also provides the foundation for further research on the regulatory functions of exosomal miRNAs in the context of ADSC osteogenesis.

• cancer therapy
• drug delivery
• exosome
• exosome engineering
• mesenchymal stem cells

• Animals
• Clinical Trials as Topic
• Drug Delivery Systems
• Exosomes/metabolism
• Humans
• Mesenchymal Stem Cells/metabolism
• Neoplasms/blood supply
• Neoplasms/therapy
• Neovascularization, Pathologic/therapy