Read the Latest Scientific Articles on Exosomes

Cardiovascular

Ticagrelor Enhances Release of Anti-Hypoxic Cardiac Progenitor Cell-Derived Exosomes Through Increasing Cell Proliferation In Vitro

Casieri et al. Scientific Reports volume 10, Article number: 2494 (2020)
  • Pro-survival exosomes from human cardiac-derived mesenchymal progenitor cells (hCPCs) is regulated by clinically relevant dose of ticagrelor (1 μM), an oral selective and reversible non-thienopyridine P2Y12 inhibitor
  • Ticagrelor-induced enhancement of exosome levels is related to increased mitotic activity of hCPCs
  • Drug-response threshold above which the effects on hCPCs are lost due to higher dose of ticagrelor and larger adenosine levels
  • Sustained pre-treatment of cardiomyocytes with exosomes released from explant-derived hCPCs exposed to low-dose ticagrelor attenuated hypoxia-induced apoptosis through acute phosphorylation of ERK42/44
  • Ticagrelor can be leveraged to modulate release of anti-hypoxic exosomes from resident hCPCs

High miR-133a levels in the circulation anticipates presentation of clinical events in familial hypercholesterolemia patients

Escate et al. Cardiovascular Research, 15 February 2020
  • A differential signature of 10 miRNA was obtained by comparing two extreme phenotypes consisting of FH-patients suffering a cardiovascular event (CVE) within a 8-year follow-up period (FH-CVE, N=42) and non-FH hypercholesterolemic relatives from the same cohort, matched for age and treatment, without CVE during the same period (nFH-nCVE, N=30)
  • miR-133a was significantly higher in FH-CVE than in FH-nCVE patients
  • High plasma miR-133a levels associated to the higher risk of presenting a CVE within the next 8 years
  • In silico analysis of curate biological interactions related miR-133a with target genes involved in regulation of the cell-membrane lipid-receptor LRP6 and inflammatory cytokines (CXCL8, IL6, TNF).
  • These predictions were experimentally proven in human macrophages and endothelial cells transfected with agomiR-133a
  • Elevated levels of miR-133a in the circulation anticipate those FH-patients that are going to present a clinical CVE within the next 2 years (average)
  • miR-133a is directly related with lipid- and inflammatory-signalling in key cells for atherosclerosis progression

Dental

Pulp-Derived Exosomes in a Fibrin-Based Regenerative Root Filling Material.

Ivica et al.(2020)J. Clin. Med. 11 February 2020
  • Human mesenchymal stem cells (MSCs) were exposed to dental pulp-derived exosomes to assess exosome uptake, cell migration, and proliferation
  • Fibrin gel (i.e., a diluted fibrin sealant), was assessed as a delivery system for the exosomes
  • Exosomes improved the proliferation of MSCs
  • Propose that pulp-derived exosomes in combination with a fibrin gel could be a powerful combination for clinical translation towards improved cell-free regenerative endodontics and thus represent a new way to fill dental hard tissues

Metabolic

Pretreatment of exosomes derived from hUCMSCs with TNF-α ameliorates acute liver failure by inhibiting the activation of NLRP3 in macrophage.

Zhang et al. Life Sciences, Volume 246, 1 April 2020, 117401.
  • TNF-α pretreated hUCMSC-exosomes can reduce serum ALT, AST and proinflammatory cytokines level and inhibit activation of NLRP3 inflammation-associated pathway proteins
  • TNF-α pretreated hUCMSC-exosomes reduces pathological liver damage caused by acute liver failure
  • Anti-inflammatory-related miRNA-299-3p is up-regulated in TNF-α-stimulated MSCs and selectively packaged into exosomes for role in exosomal treatment
  • TNF-α pretreated hUCMSC-exosomes attenuate inflammatory damage caused by ALF and promotes liver tissue repair by inhibiting the activation of the NLRP3 pathway

Infectious Disease

HIV-associated exosomes promote infection of Kaposi sarcoma-associated herpesvirus via epidermal growth factor receptor

Chen et al. Journal of Virology, 12 February 2020
  • Kaposi sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi sarcoma 24 (KS), the most common malignancy in people living with HIV/AIDS
  • Oral cavity is a major route for KSHV infection and transmission
  • Exosomes purified from either the saliva of HIV-positive individuals or culture supernatants of HIV-1-infected T cell lines promote KSHV infectivity in immortalized and primary human oral epithelial cells
  • HIV-associated saliva exosomes contain the HIV trans-activation response (TAR) element, Tat, and Nef RNAs, but do not express Tat and Nef proteins
  • TAR RNA in HIV-associated exosomes contributes to enhancing KSHV infectivity through the epidermal growth factor receptor (EGFR)
  • Cetuximab, a monoclonal neutralizing antibody to EGFR, blocks HIV-associated exosome-enhanced KSHV infection
  • Saliva containing HIV-associated exosomes is a risk factor for the enhancement of KSHV infection and that the inhibition of EGFR serves as a novel strategy for preventing KSHV infection

Musculoskeletal

Bone marrow mesenchymal stem cells-derived exosomes promote tendon regeneration by facilitating the proliferation and migration of endogenous tendon stem/progenitor cells.

Yu et al. Acta Biomaterialia, online 2020-02-04.
  • Mesenchymal stem cells (MSCs)-derived exosomes are being increasingly focused as the new biological pro-regenerative therapeutic agents for various types of tissue injury
  • Novel exosome-based therapeutic application combined with a local fibrin delivery strategy for tendon repair
  • Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) promoted the proliferation, migration and tenogenic differentiation of tendon stem/progenitor cells (TSPCs) in vitro
  • BMSCs-exos in fibrin injected into the defect area of rat patellar tendon
  • Results showed that the exosomes could be controlled-released from the fibrin, retained within the defect area, and internalized by TSPCs
  • BMSCs-exos embedded in fibrin significantly improved the histological scores, enhanced the expression of mohawk, tenomodulin, and type I collagen, as well as the mechanical properties of neotendon, and also promoted the proliferation of local TSPCs in vivo
  • Demonstrated the beneficial role of BMSCs-exos in tendon regeneration, and that fibrin-exosomes delivery system represents a successful local treatment strategy of exosomes

Integration of Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes with Hydroxyapatite-Embedded Hyaluronic Acid-Alginate Hydrogel for Bone Regeneration.

Yang et al. ACS Biomater. Sci. Eng, February 6, 2020.
  • Human umbilical cord mesenchymal stem cells-derived exosomes could effectively promote the proliferation, migration, and osteogenic differentiation of a murine calvariae preosteoblast cell line in vitro
  • Synthesized an injectable hydroxyapatite (HAP)-embedded in situ cross-linked hyaluronic acid-alginate (HA-ALG) hydrogel system to durably retain exosomes at the defect sites
  • Combined the exosomes with the HAP-embedded in situ cross-linked HA-ALG hydrogel system to repair bone defects in rats in vivo
  • Combination of exosomes and composite hydrogel could significantly enhance bone regeneration

Neurologic

Stem Cell-Derived Exosomes in Autism Spectrum Disorder.

Alessio et al. Int. J. Environ. Res. Public Health 2020, 17, 944.
  • Neuroinflammation and neuro-immune cross-talk dysregulation are specific hallmarks of ASD
  • Positive and restorative effects mediated by stem cells could be due to their paracrine activity
  • Exosomes are sub-organelles, enriched by RNA and proteins, that provide cell-to-cell communication
  • Article describes the potential role of exosomes in alleviating ASD symptoms

Engineered Exosomes With Elevated Mir-27a Improve Neurological Outcome in Ischemic Mice

Zhang et al. Stroke, Vol 51, Issue Suppl_1, February 2020
  • Augmentation of axonal growth enhances improvement of neurological function after stroke
  • In vivo study investigated whether exosomes carrying elevated miR-27a (27a-exos) enhance axonal growth and neurological outcome after stroke
  • 27a-exos were isolated from medium of mesenchymal stromal cells (MSCs) transfected with lenti-miR-27 vector
  • miR-27a (3×1011 particles) were injected intravenously into mice at 24h after middle cerebral artery occlusion (MCAO)
  • Empty-exos (n=7) significantly (p <0.05) reduced the foot-fault (5±0.1 vs 11±0.5 in control) and the times to remove adhesive paper (seconds, 47±3 vs 70±4)
  • Compared with empty-exos, 27a-exos (n=7) further significantly (p <0.05) reduced foot-fault (3.0±0.2) and times to remove the paper (38±1.7)
  • 27a-exos substantially decreased the levels of the inhibitory protein Sema6a in the YFP+ axons in peri-infarct areas
  • Tailored 27a-exos augment the therapeutic effect of exosomes on stroke recovery
  • Suppression of axonal inhibitory proteins such as Sema6a may contribute to the 27a-exo-enhanced axonal outgrowth to promote neurological recovery post stroke

Intranasal Administration of Mesenchymal Stem Cell (MSC)-Derived Exosomes Confers Acute Neuroprotection After Neonatal Stroke

Pathipati et al Stroke, Vol 51, Issue Suppl_1, February 2020
  • Delayed mesenchymal stem cell (MSC)-based therapy to be beneficial after neonatal stroke
  • Intranasal administration of MSC-derived Exo after neonatal stroke
  • Postnatal day 9 (P9) mice were subjected to a 3h middle cerebral artery occlusion (tMCAO)
  • By 24h after administration, labelled murine MSC exosomes were visible ipsilateral along the lateral ventricle, in the SVZ, corpus callosum and in the penumbra, localized largely to Glut1+-vessels and Iba1+-microglia (MG)
  • By 72h, labeled Exo were predominantly localized in Iba1+-MG peri-infarct
  • Compared to vehicle/untreated mice, intranasal Exo significantly reduced injury volume at 72h
  • MSC-Exosomes exert short-term protection against neonatal stroke
  • Magnitude of Exo uptake depends on the status of MG activation after injury

M2 Microglia Derived Exosomes Promote White Matter Repair and Long-Term Functional Recovery After Focal Cerebral Ischemia in Mice

Li et al. Stroke, Vol 51, Issue Suppl_1, February 2020
  • White matter injury aggravates neurological and cognitive impairment in experimental ischemic stroke
  • M2 microglia promote oligodendrocyte precursor cells survival and differentiation, and further enhance white matter repair
  • Exosomes were isolated from M2 microglia (M2-Exo) and unstimulated microglia as a control (M0-Exo)
  • M2-Exo and M0-Exo (100 μg) were intravenously injected after 90-minute middle cerebral artery occlusion in mice
  • M2-Exo treatment promoted sensorimotor and memory function recovery
  • Reduced brain atrophy compared to the M0-Exo control group
  • M2-Exo increased oligodendrocyte precursor cell survival under OGD in vitro
  • Exosomal miRNA sequencing and PCR identified that miR-23a-5p was enriched in M2-Exo
  • M2-Exo treatment enhanced oligodendrocyte precursor cell survival and differentiation, further promoted white matter repair and long-term functional recovery

Effects of Different Phenotypes of Microglia-Derived Exosomes on Ischemia-Reperfusion Injury

Cao et al. Stroke, Vol 51, Issue Suppl_1, February 2020
  • Under different stimuli, microglia exhibit two entirely different functional activated states, termed the pro-inflammatory (M1) phenotype and the anti-inflammatory (M2) phenotype
  • Neuronal apoptosis was examined after oxygen-glucose deprivation (OGD) treatment with different exosomes
  • M1 microglia-derived exosomes increased neuronal apoptosis after OGD treatment than OGD alone, while M2 microglia-derived exosomes attenuated neuronal apoptosis
  • M2 microglia-derived exosomes alleviated brain infarct size and neurological deficits
  • M1 microglia-derived exosomes aggravated brain damage
  • Proteomic analysis showed that the expression of complement-related proteins in M1 microglia-derived exosomes was significantly upregulated than that of M2 microglia-derived exosomes
  • M1 microglia-derived exosomes could aggravate ischemic brain injury, while M2 microglia-derived exosomes attenuated this phenomenon

Exosomes Derived From Stroke Activated Platelets Impair Cerebral Endothelial Permeability

Li et al. Stroke, Vol 51, Issue Suppl_1, February 2020
  • Stroke activated platelets damage the blood brain barrier (BBB) and promote BBB leakage
  • Primary cerebral endothelial cells harvested from healthy adult rats were treated with platelet exosomes
  • P-Exos from ischemic adult rats significantly (p <0.05) decreased

Neonatal Stroke Alters Communication of Microglial Cells With Microglia-Derived Exosomes and Microvesicles

Lecuyer et al. Stroke, Vol 51, Issue Suppl_1, February 2020
  • Microglial cells play an important role in protecting neonatal brain from acute stroke by phagocytosing dying neurons, attenuating cytokine accumulation and by protecting neurovascular integrity
  • Transient middle cerebral artery occlusion (tMCAO) was performed in postnatal day 9 (P9)
  • Uptake of MEV from injured cortex by microglia from injured cortex was significantly higher than uptake of contralateral-MEV by microglia from uninjured cortex
  • Data demonstrate selective enhancement of microglial communication with MEV from activated microglia after acute neonatal stroke

Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study

Picca et al. Journal of Clinical Medicine, 12 February 2020
  • Systemic inflammation and mitochondrial dysfunction are involved in neurodegeneration in Parkinson’s disease (PD)
  • Circulating small EVs (sEVs) from 16 older adults with PD and 12 non‐PD controls were purified and characterized
  • PD participants showed a greater amount of circulating sEVs
  • Levels of CD9 and CD63 were lower in the sEV fraction of PD
  • Lower levels of ATP5A, NDUFS3, and SDHB were detected in sEVs from PD participants
  • A mitochondrial signature was identified in circulating sEVs from older adults with PD, in association with a specific inflammatory profile

Maximum Tolerated Dose of Exosomes Derived From Mesenchymal Stem Cells via Intra-Arterial Dosing in a Rat Stroke Model

Watanabe et al. Stroke, Vol 51, Issue Suppl_1, February 2020
  • Exosome-encapsulated transfer of miRNAs promotes neurite remodeling and functional recovery of stroke in rats
  • Rats were treated with intra-arterial exosomes (10, 50 and 100ug/0.5mL), intra-arterial MSCs (1×105 cells/0.5mL) or IA phosphate-buffered saline (IAPBS) at 1 day (1D) after MCAo
  • No neurological worsening or mortality post IA exosome delivery at any dose tier
  • Neurological deficit score of intra-arterial exosomes 10ug treatment group at POD 7, 15 and 30, and intra-arterial exosomes 50ug treatment at POD 15 were significantly improved in comparison to intra-arterial PBS
  • Intra-arterial exosomes 10ug treatment group showed trend of improvement in motor coordination compared to the intra-arterial PBS/MSC/higher doses of exosome treatment groups

Mesenchymal stem cell-derived exosomes rescue oxygen-glucose deprivation-induced injury in endothelial cells.

Kong et al. Curr Neurovasc Res. 2020 Feb 13
  • Oxygen-glucose deprivation (OGD) promoted endothelial cell apoptosis, induced the release of inflammatory factors IL-1β, IL-6, and TNF-α, and inhibited cell viability
  • OGD treatment induced TLR4, and NF-κB p65 subunit phosphorylation and caspase-1 upregulation, while co-culture with MSCs could reduce the effect of OGD treatment on endothelial cells
  • Effect of MSC-derived exosomes on OGD-treated endothelial cells was similar to that of MSCs
  • MSC-derived exosomes alleviated the OGD-induced decrease in the viability of endothelial cells, and increased levels of apoptosis, inflammatory factors, and the activation of inflammatory and inflammatory focal pathways
  • Both MSCs and MSC-derived exosomes attenuated OGD-induced rat primary brain endothelial cell injury

Disrupted blood-brain barrier in 5×FAD mouse model of Alzheimer’s disease can be mimicked and repaired in vitro with neural stem cell-derived exosomes

Liu et al. Alzheimer’s disease (AD) is a devastating neurodegenerative disease and is associated with blood-brain barrier (BBB) disruption
  • BBB breakdown in the 5 × FAD mouse model occurred at 4 months of age, which could be mimicked with an in vitro BBB model
  • Treatment of the in vitro BBB model with neural stem cell-derived exosomes reversed AD-caused BBB deficiency.

Cancer

Exosomes derived from bone marrow mesenchymal stem cells promote osteosarcoma development by activating oncogenic autophagy.

Huang et al. Journal of Bone Oncology, Volume 21, April 2020.
  • BMSC-Exos promote malignant tumorigenesis and metastasis in osteosarcoma cells
  • BMSC-Exos promotes oncogenic autophagy in osteosarcoma cells
  • BMSC-derived exosomes promote osteosarcoma cell proliferation, migration, and invasion
  • Silencing autophagy-related gene 5 (ATG5) in osteosarcoma cells abolishes the pro-tumor effects of hBMSC-Exos in vitro and in vivo
  • BMSC-Exos-mediated autophagy contributes to the BMSC-Exos-induced malignant tumorigenesis and metastasis in osteosarcoma cells

An Electrochemical Biosensor Designed by Using Zr-Based Metal–Organic Frameworks for the Detection of Glioblastoma-Derived Exosomes with Practical Application.

Sun et al. Analytical Chemistry, February 6, 2020.
  • Glioblastoma (GBM) derived specific exosomes can cross the BBB and circulate in body fluids, so they can be noninvasive biomarkers for the early diagnosis
  • Sensitive and label-free electrochemical biosensor designed by using Zr-based metal–organic frameworks (Zr-MOFs) for the detection of GBM-derived exosomes
  • Peptide ligand can specifically bind with human epidermal growth factor receptor (EGFR) and EGFR variant (v) III mutation (EGFRvIII), which are overexpressed on the GBM-derived exosomes
  • Zr-MOFs encapsulated with methylene blue can absorb on the surface of the exosomes due to the interaction between Zr4+ and the intrinsic phosphate groups outside of exosomes
  • Concentration of exosomes can be directly quantified by monitoring the electroactive molecules inside MOFs, ranging from 9.5 × 103 to 1.9 × 107 particles/μL with the detection of limit of 7.83 × 103 particles/μL
  • Biosensor can distinguish GBM patients from healthy groups, demonstrating the great prospect for early clinical diagnosis

Exosomes as potential sources of biomarkers in colorectal cancer.

Xiao et al. Cancer Letters, Volume 476, 28 April 2020, Pages 13-22.
  • Differentially expressed RNAs and proteins in exosomes play key roles in the initiation and development of CRC and are potential candidates for malignancy detection
  • Summary of the important roles of exosomes as biomarkers in CRC diagnosis, as well as the application in the metastasis, chemoresistance, and recrudescence of CRC
  • Discussion of prospects and limitations of exosomes as tumor markers

Exosomes and Lung cancer: Roles in pathophysiology, diagnosis and therapeutic applications.

Amiri et al Curr Med Chem. 2020 Feb 4.
  • Therapeutic approaches for the treatment of lung cancer, including radiotherapy and chemotherapy, are not particularly effective partly due late diagnosis
  • Exosomes cargos could be used as new diagnostic, prognostic and therapeutic biomarkers in the treatment of lung cancer
  • Use of exosomes as drug delivery systems and as cancer vaccines is under investigation

RNA sequencing of exosomes revealed differentially expressed long noncoding RNAs in early-stage esophageal squamous cell carcinoma and benign esophagitis

Tian et al. Epigenomics, 11 Feb 2020
  • Exosomal lncRNAs were analyzed using RNA-seq and validated by quantitative real-time PCR, loss-of-function, co-culture and RNA pulldown assays in in early-stage esophageal squamous cell carcinoma (ESCC) and benign esophagitis
  • 152 exosomal lncRNAs were differentially expressed between ESCC and controls
  • 124 exosomal lncRNAs were dysregulated between ESCC and esophagitis
  • Knockdown of 13 ESCC-associated lncRNAs modified proliferation, migration, and apoptosis of ESCC cells
  • A novel lncRNA RP5-1092A11.2 was highly expressed in ESCC-derived exosomes, ESCC cells and tumor tissues
  • Exosomes released from RP5-1092A11.2-knockdown cells inhibited ESCC cell proliferation
  • Dysregulated exosomal lncRNAs were functionally associated with different disease status in esophagus

Exosomes mediate intercellular transfer of non‐autonomous tolerance to proteasome inhibitors in mixed‐lineage leukemia

Ge et al. Cancer Reports, 14 February 2020
  • Proteasome inhibitors significantly improve cancer outcomes, but their use is eventually followed by proteasome inhibitor resistance and relapse
  • Proteasome inhibitor tolerance can be transmitted non‐autonomously through exosome‐mediated intercellular interactions
  • Reversible proteasome inhibitor resistance can be transmitted from cells under therapy stress to naïve sensitive cells through exosome‐mediated cell cycle arrest and enhanced stemness in mixed‐lineage leukemia cells
  • Identified several candidate exosomal proteins that may serve as predictors for proteasome inhibitor resistance and potential therapeutic targets for treating refractory mixed‐lineage leukemias
  • Inhibiting the secretion of exosomes is a promising strategy for reversing proteasome inhibitor resistance in vivo

miR-221-3p Delivered by BMMSC-Derived Microvesicles Promotes the Development of Acute Myelocytic Leukemia

Zhang et al. Front. Bioeng. Biotechnol., 14 February 2020
  • Morphology of BMMSC-derived MVs was observed under an electron microscope, and the positional relation of MVs and OCI-AML2 cells was observed by a fluorescence microscope
  • MTT, Transwell, and flow cytometry assays were used to analyze the effects of MVs on OCI-AML2 cells
  • Targeted relationship between miR-221-3p and CDKN1C was detected by dual luciferase assay
  • Verified that miR-221-3p promoted the proliferation, invasion and migration of OCI-AML2 cells, and induced the cell cycle arrest in G1/S phase as well as inhibited cell apoptosis
  • MVs promoted the proliferation, migration and invasion of AML, and induced the cell cycle arrest in G1/S phase through miR-221-3p
  • Confirmed that miR-221-3p can directly target CDKN1C to regulate cell cycle, proliferation and invasion of AML

Circular RNAs in exosomes derived from breast cancer: Promising biomarkers for diagnosis and prognosis of triple negative breast cancer (TNBC)

Yang et al.
  • A combinative strategy of RNA-sequencing (RNA-seq) technique, RT-qPCR and bioinformatic analysis was employed to unearth the potential mechanism of differential circRNAs in serum-exosomes (n=20) and tissues (n=20) from TNBC patients
  • has-circRNA-LPXN was down-regulated and has-circRNA-HSDL2 was up-regulated, which was valuable for breast cancer diagnosis by analyzing these circRNAs in serum-exosomes from BCa patients compared with healthy people
  • Expression levels of has-circRNA-LPXN and has-circRNA-HSDL2 were found significantly different both in serum-exosomes and tissues of TNBC and these circRNAs might function as competing endogenous RNAs and play vital roles in the development of TNBC

Otolaryngology

Exosomes mediate sensory hair cell protection in the inner ear.

Breglio et al. Journal of Clinical Investigation, February 6, 2020.
  • Hair cells are the mechanosensory receptors of the inner ear, responsible for hearing and balance
  • Hair cell death and consequent hearing loss are common results of treatment with ototoxic drugs
  • In response to heat stress, inner ear tissue releases exosomes that carry HSP70
  • Isolated exosomes from heat-shocked utricles were sufficient to improve survival of hair cells exposed to the aminoglycoside antibiotic neomycin
  • Exosomes are a previously undescribed mechanism of intercellular communication in the inner ear that can mediate non-autonomous hair cell survival