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Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary Success

BIOMEDICINES (2021)

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Article Engineering, Biomedical

Extracellular vesicles from three dimensional culture of human placental mesenchymal stem cells ameliorated renal ischemia/reperfusion injury

Xuefeng Zhang et al.

Summary: This study demonstrated that extracellular vesicles (EVs) from 3D culture of human placental MSCs (hPMSCs) showed greater therapeutic potential for ischemia-reperfusion acute kidney injury (I/R-AKI) compared to EVs from 2D culture. The EVs from 3D culture were more effective in protecting against cell death and inflammation, leading to reduced tissue damage and improved renal function. MicroRNA profiling analysis revealed significant changes in EVs from 3D culture, particularly in the expression of miR-93-5p.

INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS (2022)

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Article Clinical Neurology

Extracellular Vesicles Derived from Neural Progenitor Cells--a Preclinical Evaluation for Stroke Treatment in Mice

X. Zheng et al.

Summary: Stem cells such as mesenchymal stem cells (MSCs) enhance neurological recovery in preclinical stroke models by secreting extracellular vesicles (EVs), with neural progenitor cells (NPCs)-derived EVs showing therapeutic potential in reducing cell injury and promoting neuroregeneration in mice post-stroke. NPC-EVs delivery leads to increased blood concentrations of B and T lymphocytes without affecting cerebral cell counts, suggesting a potential contribution to reverting post-stroke immunosuppression. Furthermore, biodistribution analysis reveals the majority of NPC-EVs to be found in extracranial organs like the liver and lung after systemic administration.

TRANSLATIONAL STROKE RESEARCH (2021)

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Article Cardiac & Cardiovascular Systems

Gene-modified Exosomes Protect the Brain Against Prolonged Deep Hypothermic Circulatory Arrest

Jiang Shi et al.

Summary: Exosomes derived from bone marrow mesenchymal stem cells (MSCs) provide powerful neuroprotection against cerebral injury induced by deep hypothermic circulatory arrest (DHCA), and this neuroprotection can be further enhanced by overexpressing miR-214. Pre-treatment with miR-214-enriched exosomes improves neurological functions in rats and increases the survival rate of neurons in the hippocampus.

ANNALS OF THORACIC SURGERY (2021)

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Article Chemistry, Multidisciplinary

Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Mitochondrial Damage and Inflammation by Stabilizing Mitochondrial DNA

Meng Zhao et al.

Summary: The study demonstrates that MSC-EVs can alleviate mtDNA damage and inflammation after acute kidney injury, with their effects partially dependent on the TFAM signaling pathway. This suggests that MSC-EVs are promising nanotherapeutics for diseases characterized by mitochondrial damage, highlighting the essential role of TFAM in maintaining their regenerative capacity.

ACS NANO (2021)

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Article Medicine, Research & Experimental

Mesenchymal stem cell-derived extracellular vesicles promote microglial M2 polarization after subarachnoid hemorrhage in rats and involve the AMPK/NF-κB signaling pathway

Min Han et al.

Summary: MSCs-EVs show neuroprotective effects in a rat SAH model by modulating neuroinflammation and microglial polarization. These effects may be mediated through downregulation of inflammatory cytokines and NF-kappa B, activation of AMPK, and regulation of immune response-related gene expression.

BIOMEDICINE & PHARMACOTHERAPY (2021)

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Article Cell Biology

Bone marrow mesenchymal stem cells-derived exosomes reduce Aβ deposition and improve cognitive function recovery in mice with Alzheimer's disease by activating sphingosine kinase/sphingosine-1-phosphate signaling pathway

Xinhui Wang et al.

Summary: Exosomes play a role in the development and progression of Alzheimer's disease, with potential to reduce A beta deposition and promote cognitive function recovery in AD mice by activating the SphK/S1P signaling pathway. This suggests that exosomes containing S1P/SphK could be explored as a potential AD cure.

CELL BIOLOGY INTERNATIONAL (2021)

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Article Biochemistry & Molecular Biology

Mesenchymal stem cell (MSC)-derived exosomes as a cell-free therapy for patients Infected with COVID-19: Real opportunities and range of promises

Leila Rezakhani et al.

Summary: Currently, there is a lack of effective antiviral medications or vaccines available for COVID-19, highlighting the urgent need for new treatment options. Inflammation induced by the virus often leads to acute respiratory distress syndrome (ARDS), emphasizing the importance of controlling inflammation. Research suggests that using mesenchymal stem cells and exosomes could potentially help suppress inflammation.

CHEMISTRY AND PHYSICS OF LIPIDS (2021)

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Article Respiratory System

Mesenchymal stromal cell extracellular vesicles rescue mitochondrial dysfunction and improve barrier integrity in clinically relevant models of ARDS

Johnatas Dutra Silva et al.

Summary: In acute respiratory distress syndrome (ARDS), mitochondrial dysfunction contributes to damage of the alveolar epithelial and endothelial barriers. Mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) can improve alveolar-capillary barrier integrity through mitochondrial transfer, restoring normal barrier properties and mitochondrial functions in a model of ARDS.

EUROPEAN RESPIRATORY JOURNAL (2021)

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Article Cell Biology

Mesenchymal stem cell-derived extracellular vesicles conditionally ameliorate bone marrow failure symptoms in an immune-mediated aplastic anemia mouse model

Mohammad A. Gholampour et al.

Summary: The study showed that treatment with hypoxic MSC-EVs and normoxic MSC-EVs significantly prolonged the survival rate, increased platelet counts, and ameliorated BM hypoplasia in a mouse model of AA. The effects of MSC-EVs were mediated by T cell suppression and inhibition of interferon-gamma and tumor necrosis factor-alpha production. Additionally, there was an association between reduced pro-inflammatory cytokine levels and decreased splenocyte viability in vitro.

JOURNAL OF CELLULAR PHYSIOLOGY (2021)

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Article Immunology

Umbilical cord mesenchymal stem cells as well as their released exosomes suppress proliferation of activated PBMCs in multiple sclerosis

Hussein Baharlooi et al.

Summary: This study showed that MSCs and their exosomes have suppressive effects on PBMC proliferation in patients with multiple sclerosis. Exosomes from MSCs had a more significant suppression effect compared to MSCs. However, the suppression capacity of both MSCs and exosomes decreased significantly during extensive sub-culturing.

SCANDINAVIAN JOURNAL OF IMMUNOLOGY (2021)

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Article Multidisciplinary Sciences

Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation

Debora Giunti et al.

Summary: MSCs exhibit neuroprotective, immunomodulatory, and neuroregenerative properties, releasing extracellular vesicles containing miRNAs to modulate the inflammatory phenotype of microglia and potentially impact neuroinflammation.

SCIENTIFIC REPORTS (2021)

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Review Cell & Tissue Engineering

Mesenchymal stem cell-derived small extracellular vesicles in the treatment of human diseases: Progress and prospect

Jie Shi et al.

Summary: Mesenchymal stem cell-derived small extracellular vesicles (sEVs) have shown great potential in treating a variety of diseases, exhibiting properties such as stability in circulation, good biocompatibility, and low toxicity and immunogenicity. They are considered as attractive agents for therapy, with emerging evidence suggesting their efficacy may even surpass that of MSCs in certain diseases.

WORLD JOURNAL OF STEM CELLS (2021)

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Article Cell Biology

Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2/Bcl2 Axis

Jun Han et al.

Summary: The study demonstrates that microRNA-410 derived from mesenchymal stem cell-derived extracellular vesicles can protect against hypoxia-ischemia brain damage by modulating signaling pathways related to neuronal apoptosis.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Gastroenterology & Hepatology

The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future

Yusuke Watanabe et al.

Summary: Cirrhosis is a chronic liver condition that can lead to liver failure, with current treatment options primarily being liver transplantation or cell-based therapy. However, challenges such as limitations on cell quantity and infiltration into target organs have hindered the widespread adoption of cell-based therapy. As a result, researchers are now turning their focus towards cell-free therapy using extracellular vesicles or exosomes as a potential alternative.

CLINICAL AND MOLECULAR HEPATOLOGY (2021)

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Review Pathology

Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles as novel cell-free therapy for treatment of autoimmune disorders

Fatemeh Rezaei Kahmini et al.

Summary: MSC-derived EVs are considered to be safer and more effective than MSCs themselves, offering a potentially more effective treatment strategy for overcoming limitations and challenges observed in MSC therapy. This alternative approach may present a promising avenue for the treatment of autoimmune diseases.

EXPERIMENTAL AND MOLECULAR PATHOLOGY (2021)

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Review Biochemistry & Molecular Biology

Ancient Evolutionary Origin and Properties of Universally Produced Natural Exosomes Contribute to Their Therapeutic Superiority Compared to Artificial Nanoparticles

Phillip W. Askenase

Summary: Extracellular vesicles, specifically exosomes, play crucial roles in biological processes and clinical diseases, with their potential therapeutic applications requiring further exploration. Their evolutionary origins and unique properties make them promising candidates for therapies compared to artificial nanoparticles.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Oncology

Challenges and advances in clinical applications of mesenchymal stromal cells

Tian Zhou et al.

Summary: MSC therapy for clinical applications faces challenges due to inconsistent criteria for MSCs identity and their inherited heterogeneity. Strategies have been developed to overcome these challenges with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Review Pharmacology & Pharmacy

Stem Cell Therapies in Alzheimer's Disease: Applications for Disease Modeling

Zizhen Si et al.

Summary: Alzheimer's disease is a neurodegenerative disease with no effective treatment currently available. Stem cell technologies including iPSCs, NSCs, and MSCs show promising therapeutic strategies for AD. These developing stem cell technologies hold considerable promise to combat AD and other neurodegenerative disorders.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2021)

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Review Neurosciences

Extracellular Vesicles as an Emerging Frontier in Spinal Cord Injury Pathobiology and Therapy

Dipankar Dutta et al.

Summary: Extracellular vesicles (EVs) are membrane-delimited particles secreted by nearly all cell types, playing crucial roles in mediating physiological functions and pathophysiological processes in the central nervous system. Research has shown that EVs are important in neurotrauma such as spinal cord injury (SCI) and may serve as potential targets for therapy.

TRENDS IN NEUROSCIENCES (2021)

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Review Pharmacology & Pharmacy

Biological Cells as Therapeutic Delivery Vehicles

Lucas M. Bush et al.

Summary: Live cells have innate targeting mechanisms and can be used as drug-delivery vehicles to increase drug accumulation efficiency. In cases where native cell types do not exhibit the desired therapeutic phenotype, preferred outcomes can be achieved by genetically modifying and reprogramming cells. Recent advances in using cells like red blood cells, platelets, neutrophils, mesenchymal stem cells, and bacteria for drug delivery have been highlighted in this review.

TRENDS IN PHARMACOLOGICAL SCIENCES (2021)

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Review Immunology

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cells and Extracellular Vesicles: Therapeutic Outlook for Inflammatory and Degenerative Diseases

Sylwia Dabrowska et al.

Summary: Mesenchymal stem cells (MSCs) possess supportive, differentiating, and immunoregulatory functions, while the extracellular vesicles (EVs) they produce can serve as a potential cellular therapy tool.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Biochemistry & Molecular Biology

News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Jacopo Meldolesi

Summary: Biomarkers play an important role in biology and medicine, aiding in studying the origin and development of diseases. Currently, research mainly focuses on using biomarkers to study Alzheimer's and other neurodegenerative diseases, with fluid biomarkers and imaging biomarkers being the two main types. The widespread use of biomarkers has advanced medical diagnosis, prognosis, and treatment methods.

BIOMEDICINES (2021)

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Article Cell Biology

Mesenchymal stem cell-derived extracellular vesicles reduce senescence and extend health span in mouse models of aging

Akaitz Dorronsoro et al.

Summary: The injection of BM-MSCs from young mice can prolong lifespan and healthspan, while conditioned media (CM) from young BM-MSCs can rescue the function of aged stem cells and senescent fibroblasts. Extracellular vesicles (EVs) from young BM-MSC CM can extend lifespan in mice, and EVs from MSCs generated from human ES cells can reduce senescence and improve healthspan.

AGING CELL (2021)

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Article Cell & Tissue Engineering

Critical considerations for the development of potency tests for therapeutic applications of mesenchymal stromal cell-derived small extracellular vesicles

Mario Gimona et al.

Summary: Mesenchymal stromal/stem cells (MSCs) have been approved for treating certain diseases through paracrine secretion of small extracellular vesicles (sEVs). Despite the potential advantages of sEV preparations over cellular MSC products, there are challenges in developing MSC-sEV drug products, including establishing quality control metrics and developing effective potency assays.

CYTOTHERAPY (2021)

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Article Cell Biology

Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication

Gustavo Garcia et al.

Summary: A novel medium-throughput drug-screening system was developed to identify potential drug candidates that can effectively inhibit SARS-CoV-2 infection. Through drug-protein interaction-based screening, promising kinase inhibitors were discovered as host-directed therapy for treating coronavirus infections, highlighting important mechanisms of host-pathogen interactions.

CELL REPORTS (2021)

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Article Cell Biology

Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2

Mark Dittmar et al.

Summary: There is an urgent need for antiviral drugs to treat SARS-CoV-2, and screening has identified several potential candidates with different mechanisms of action in lung epithelial cells. Some of these drugs could be used for the treatment of respiratory cells in patients.

CELL REPORTS (2021)

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Review Biochemistry & Molecular Biology

Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

Jacopo Meldolesi

Summary: Neurons, astrocytes and microglia cooperate intensely through the release/binding of signaling factors, direct surface binding, and generation/release of extracellular vesicles. These vesicles, with extraordinary properties, play critical roles in various brain diseases by fusing with distinct target cells and releasing cargos containing essential molecules like proteins and miRNAs. The differences in vesicle trafficking contribute to the progression and development of diseases such as multiple sclerosis and Alzheimer's disease, highlighting the importance of vesicles as potential biomarkers for diagnostic and therapeutic advancements in the future.

MOLECULAR BIOMEDICINE (2021)

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Review Cell Biology

Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications

Wei-Zhan Zhuang et al.

Summary: Mesenchymal stem/stromal cells (MSCs) are a promising resource for cell-based therapy due to their high immunomodulation ability and tropism towards inflamed and injured tissues. However, the lack of standardized methods to evaluate the safety, efficacy, and biodistribution of MSCs has been a major hindrance to their clinical application.

JOURNAL OF BIOMEDICAL SCIENCE (2021)

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Article Cell & Tissue Engineering

Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying miRNA as a Potential Multi Target Therapy to COVID-19: an In Silico Analysis

Iago Carvalho Schultz et al.

Summary: The study suggests that MSC-derived EVs may have the potential to modulate exacerbated cytokines, cell death, and coagulation disturbances in severe COVID-19, thereby preventing tissue damage.

STEM CELL REVIEWS AND REPORTS (2021)

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Article Cell & Tissue Engineering

The role of small extracellular vesicles in cerebral and myocardial ischemia-Molecular signals, treatment targets, and future clinical translation

Xuan Zheng et al.

Summary: The heart and brain form a functional axis that is disrupted under ischemic conditions, but stem cell-derived extracellular vesicles show potential for treating ischemic stroke and myocardial infarction, offering hope. Therapeutic actions of EVs in the brain and heart reciprocally influence each other, with EVs playing roles in promoting angiogenesis, parenchymal remodeling, and tissue recovery, and the therapeutic effects are dependent on the cargos within EVs.

STEM CELLS (2021)

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Article Cell & Tissue Engineering

Proposed Mechanisms of Targeting COVID-19 by Delivering Mesenchymal Stem Cells and Their Exosomes to Damaged Organs

Elham Jamshidi et al.

Summary: In the face of the unprecedented challenge presented by the COVID-19 pandemic, developing effective treatments using MSCs and their exosomes, which have been shown to possess therapeutic potential through immunomodulation and organ repair, is crucial. Research focus has also been on the delivery routes and modifications of MSCs for safe and effective administration in COVID-19. Recent advances in clinical trials suggest promising therapeutic potential of MSCs and their exosomes in treating COVID-19.

STEM CELL REVIEWS AND REPORTS (2021)

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Article Cell & Tissue Engineering

Regenerative Medicine in COVID-19 Treatment: Real Opportunities and Range of Promises

Arefeh Basiri et al.

Summary: The COVID-19 pandemic has raised global concerns, with regenerative medicine presenting potential impact on disease management through therapies like stem cells and NK cells. Cell products such as exosomes have shown therapeutic effects as well. There is currently no specific cure, but regenerative medicine offers new possibilities for the treatment of COVID-19.

STEM CELL REVIEWS AND REPORTS (2021)

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Review Cell Biology

Mesenchymal stromal cell-derived extracellular vesicles as cell-free biologics for the ex vivo expansion of hematopoietic stem cells

Pallavi Budgude et al.

CELL BIOLOGY INTERNATIONAL (2020)

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Article Immunology

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Novel Cell-Free Therapy

Morteza Jafarinia et al.

IMMUNOLOGICAL INVESTIGATIONS (2020)

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Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies-Synthetic Review

Joanna Lelek et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Current Knowledge and Future Perspectives on Mesenchymal Stem Cell-Derived Exosomes as a New Therapeutic Agent

Hyeon Su Joo et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Free and hydrogel encapsulated exosome-based therapies in regenerative medicine

Ali Akbari et al.

LIFE SCIENCES (2020)

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Review Cell Biology

Mesenchymal Stem Cell Derived Extracellular Vesicles in Aging

Jeremy Boulestreau et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2020)

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International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19

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Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine?

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Adipose mesenchymal stem cell-derived extracellular vesicles containing microRNA-26a-5p target TLR4 and protect against diabetic nephropathy

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Mesenchymal Stem Cell Derived Biocompatible Membrane Vesicles Demonstrate Immunomodulatory Activity Inhibiting Activation and proliferation of Human Mononuclear Cells

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Bone regeneration is mediated by macrophage extracellular vesicles

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Transfer of microRNA-221 from mesenchymal stem cell-derived extracellular vesicles inhibits atherosclerotic plaque formation

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Bone marrow-derived mesenchymal stem cells improve cognitive impairment in an Alzheimer's disease model by increasing the expression of microRNA-146a in hippocampus

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Protective effect of miRNA-containing extracellular vesicles derived from mesenchymal stromal cells of old rats on renal function in chronic kidney disease

Yan Wang et al.

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Article Neurosciences

Mesenchymal Stem Cell-Conditioned Medium Improves Mitochondrial Dysfunction and Suppresses Apoptosis in Okadaic Acid-Treated SH-SY5Y Cells by Extracellular Vesicle Mitochondrial Transfer

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Strategies for scalable manufacturing and translation of MSC-derived extracellular vesicles

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Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential

Na Song et al.

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Rejuvenation of mesenchymal stem cells by extracellular vesicles inhibits the elevation of reactive oxygen species

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Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization

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Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review

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MiRNA Profiles of Extracellular Vesicles Secreted by Mesenchymal Stromal Cells-Can They Predict Potential Off-Target Effects?

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Osteoblastogenesis Alters Small RNA Profiles in EVs Derived from Bone Marrow Stem Cells (BMSCs) and Adipose Stem Cells (ASCs)

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Microvesicles (MIVs) secreted from adipose-derived stem cells (ADSCs) contain multiple microRNAs and promote the migration and invasion of endothelial cells

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Mesenchymal stromal cell-derived exosomes attenuatemyocardial ischaemia-reperfusion injury throughmiR-182-regulated macrophage polarization

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ANNALS OF TRANSLATIONAL MEDICINE (2019)

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Exosomes and Ectosomes in Intercellular Communication

Jacopo Meldolesi

CURRENT BIOLOGY (2018)

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NATURE REVIEWS MOLECULAR CELL BIOLOGY (2018)

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Mesenchymal stem cell-derived extracellular vesicles affect disease outcomes via transfer of microRNAs

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STEM CELL RESEARCH & THERAPY (2018)

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Regenerative abilities of mesenchymal stem cells through mitochondrial transfer

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Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction

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THERANOSTICS (2018)

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Review Cell & Tissue Engineering

A Comprehensive Review on Exosomes and Microvesicles as Epigenetic Factors

Behnaz Bakhshandeh et al.

CURRENT STEM CELL RESEARCH & THERAPY (2017)

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2017)

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Extracellular vesicle communication pathways as regulatory targets of oncogenic transformation

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SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2017)

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Non-coding RNAs in Mesenchymal Stem Cell-Derived Extracellular Vesicles: Deciphering Regulatory Roles in Stem Cell Potency, Inflammatory Resolve, and Tissue Regeneration

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FRONTIERS IN GENETICS (2017)

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Review Cell & Tissue Engineering

Extracellular Vesicles: Evolving Factors in Stem Cell Biology

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STEM CELLS INTERNATIONAL (2016)

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Article Cell & Tissue Engineering

Mesenchymal Stem Cells Secrete Immunologically Active Exosomes

Bin Zhang et al.

STEM CELLS AND DEVELOPMENT (2014)

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Review Cell Biology

Extracellular vesicles: Exosomes, microvesicles, and friends

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Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms

T Kinnaird et al.

CIRCULATION RESEARCH (2004)

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Article Biochemistry & Molecular Biology

Mesenchymal stem cells: Will they have a role in the clinic?

SM Devine

JOURNAL OF CELLULAR BIOCHEMISTRY (2002)

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Adult bone marrow stem cells for cell and gene therapies: Implications for greater use

CB Ballas et al.

JOURNAL OF CELLULAR BIOCHEMISTRY (2002)

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Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart

C Toma et al.

CIRCULATION (2002)

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