Central Nervous System Cell‐Derived Exosomes in Neurodegenerative Diseases

Tian, Yang; Fu, Chen; Wu, Yifan; Lu, Yao; Liu, Xuemei; Zhang, Yunling

doi:10.1155/2021/9965564

Cited by 16 publications

(14 citation statements)

References 107 publications

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“…A lot of focus has been given to exosomes in neurodegenerative diseases, e.g., neuronal, astrocytic and oligodendrocytic exosomes [ 40 – 43 ], while the utility of other EV subtypes as biomarkers of neurodegenerative diseases has not yet been fully elucidated and requires further attention. Little evidence is available in the literature for MV alterations in neurodegeneration [ 44 ].…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

Younas

Flores

Hopfner

et al. 2022

Transl Neurodegener

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Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood–brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.

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Section: Extracellular Vesiclesmentioning

confidence: 99%

A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

Younas

Flores

Hopfner

et al. 2022

Transl Neurodegener

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“…Exosomes represent a subspecies of extracellular vesicles (EVs) with structural size ranging from 30 to 150 nm, released from most cells in all living systems. They exist in various body fluids, such as cerebral spinal fluid, blood, saliva, and urine [ 28 , 29 , 30 , 31 ]. Exosomes are initiated by the invagination of the endosomal membrane ( Figure 1 ).…”

Section: Characteristics Of Exosomesmentioning

confidence: 99%

Potential Role of Exosomes in Ischemic Stroke Treatment

Jiang

Chen

et al. 2022

Biomolecules

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Ischemic stroke is a life-threatening cerebral vascular disease and accounts for high disability and mortality worldwide. Currently, no efficient therapeutic strategies are available for promoting neurological recovery in clinical practice, except rehabilitation. The majority of neuroprotective drugs showed positive impact in pre-clinical studies but failed in clinical trials. Therefore, there is an urgent demand for new promising therapeutic approaches for ischemic stroke treatment. Emerging evidence suggests that exosomes mediate communication between cells in both physiological and pathological conditions. Exosomes have received extensive attention for therapy following a stroke, because of their unique characteristics, such as the ability to cross the blood brain–barrier, low immunogenicity, and low toxicity. An increasing number of studies have demonstrated positively neurorestorative effects of exosome-based therapy, which are largely mediated by the microRNA cargo. Herein, we review the current knowledge of exosomes, the relationships between exosomes and stroke, and the therapeutic effects of exosome-based treatments in neurovascular remodeling processes after stroke. Exosomes provide a viable and prospective treatment strategy for ischemic stroke patients.

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“…The beneficial effects exerted by MSC-exosomes have been highlighted in different Central Nervous System (CNS) and peripheral nerve injuries animal studies [2,[28][29][30][31][32][33]. In respect to ocular diseases, the therapeutic effects of EVs including their wound healing capacity and angiogenesis effects have been under the spotlight recently [34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Bone marrow mesenchymal stromal cells in a 3D system produce higher concentration of extracellular vesicles (EVs) with increased complexity and enhanced neuronal growth properties

et al. 2022

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Purpose Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have been demonstrated to possess great potential in preclinical models. An efficient biomanufacturing platform is necessary for scale up production for clinical therapeutic applications. The aim of this study is to investigate the potential differences in neuro-regenerative properties of MSC-derived EVs generated in 2D versus 3D culture systems. Method Human bone marrow MSCs (BM-MSCs) were cultured in 2D monolayer and 3D bioreactor systems. EVs were isolated using ultracentrifugation followed by size and concentration measurements utilizing dynamic light scattering (NanoSight) and by fluorescence staining (ExoView). Mouse trigeminal ganglia (TG) neurons were isolated from BALB/c mice and cultured in the presence or absence of EVs derived from 2D or 3D culture systems. Neuronal growth and morphology were monitored over 5 days followed by immunostaining for β3 tubulin. Confocal images were analyzed by Neurolucida software to obtain the density and length of the neurites. Results The NanoSight tracking analysis revealed a remarkable increase (24-fold change) in the concentration of EVs obtained from the 3D versus 2D culture condition. ExoView analysis showed a significantly higher concentration of CD63, CD81, and CD9 markers in the EVs derived from 3D versus 2D conditions. Furthermore, a notable shift toward a more heterogeneous phenotype was observed in the 3D-derived EVs compared to those from 2D culture systems. EVs derived from both culture conditions remarkably induced neurite growth and elongation after 5 days in culture compared to untreated control. Neurolucida analysis of the immunostaining images (β3 tubulin) showed a significant increase in neurite length in TG neurons treated with 3D- versus 2D-derived EVs (3301.5 μm vs. 1860.5 μm, P < 0.05). Finally, Sholl analysis demonstrated a significant increase in complexity of the neuronal growth in neurons treated with 3D- versus 2D-derived EVs (P < 0.05). Conclusion This study highlights considerable differences in EVs obtained from different culture microenvironments, which could have implications for their therapeutic effects and potency. The 3D culture system seems to provide a preferred environment that modulates the paracrine function of the cells and the release of a higher number of EVs with enhanced biophysical properties and functions in the context of neurite elongation and growth.

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Central Nervous System Cell‐Derived Exosomes in Neurodegenerative Diseases

Cited by 16 publications

References 107 publications

A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

Potential Role of Exosomes in Ischemic Stroke Treatment

Bone marrow mesenchymal stromal cells in a 3D system produce higher concentration of extracellular vesicles (EVs) with increased complexity and enhanced neuronal growth properties

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