Time-Dependent Memory and Gait Improvement by Intranasally-Administered Extracellular Vesicles in Parkinson’s Disease Model Rats

Narbute, Karīna; Piļipenko, Vladimirs; Pupure, Jolanta; Klinovičs, Toms; Auders, Jānis; Jonavičė, Ugnė; Kriaučiūnaitė, Karolina; Pivoriūnas, Augustas; Kluša, Vija

doi:10.1007/s10571-020-00865-8

Cited by 13 publications

(8 citation statements)

References 22 publications

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“…IN administration of EVs provides an effective strategy to treat a variety of CNS pathologies, including neurodegenerative diseases such as Parkinson's disease (PD), 44 MS, 34 and Alzheimer's disease (AD), 45‐47 psychiatric disorders including autism 32,48 and schizophrenia, 49 and neurotrauma such as that caused by perinatal brain injury, 50 status epilepticus (SE), 42,51 and traumatic brain damage (TBI) 52 …”

Section: Treatment Of Cns Disorders By Nasal Administrationmentioning

confidence: 99%

Intranasal Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles for the Treatment of Neurological Diseases

2021

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Neurological disorders are diseases of the central nervous system (CNS), characterized by a progressive degeneration of cells and deficiencies in neural functions. Mesenchymal stem cells (MSCs) are a promising therapy for diseases and disorders of the CNS. Increasing evidence suggests that their beneficial abilities can be attributed to their paracrine secretion of extracellular vesicles (EVs). Administration of EVs that contain a mixture of proteins, lipids, and nucleic acids, resembling the secretome of MSCs, has been shown to mimic most of the effects of the parental cells. Moreover, the small size and safety profile of EVs provide a number of advantages over cell transplantation. Intranasal (IN) administration of EVs has been established as an effective and reliable way to bypass the blood-brain barrier and deliver drugs to the CNS. In addition to pharmacological drugs, EVs can be loaded with a diverse range of cargo designed to modulate gene expression and protein functions in recipient cells, and lead to immunomodulation, neurogenesis, neuroprotection, and degradation of protein aggregates. In this review, we will explore the proposed physiological pathways by which EVs migrate through the nasal route to the CNS where they can actively target a region of injury or inflammation and exert their therapeutic effects. We will summarize the functional outcomes observed in animal models of neurological diseases following IN treatment with MSC-derived EVs. We will also examine key mechanisms that have been suggested to mediate the beneficial effects of EV-based therapy.

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Section: Treatment Of Cns Disorders By Nasal Administrationmentioning

confidence: 99%

Intranasal Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles for the Treatment of Neurological Diseases

2021

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“…At the same time myelin-associated growth inhibitors are released through exosomes from oligodendrocytes [ 195 ]. Therefore, active production of exosomes in the injuries areas of CNS may have a strong effect on CNS neuroplasticity, including collateral sprouting and unmasking of latent synapses [ 196 , 197 ].…”

Section: Evs In Axon Regenerationmentioning

confidence: 99%

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

Anđjus

Kosanović

Milićević

et al. 2020

IJMS

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Extracellular vesicles (EVs) have recently attracted a great deal of interest as they may represent a new biosignaling paradigm. According to the mode of biogenesis, size and composition, two broad categories of EVs have been described, exosomes and microvesicles. EVs have been shown to carry cargoes of signaling proteins, RNA species, DNA and lipids. Once released, their content is selectively taken up by near or distant target cells, influencing their behavior. Exosomes are involved in cell–cell communication in a wide range of embryonic developmental processes and in fetal–maternal communication. In the present review, an outline of the role of EVs in neural development, regeneration and diseases is presented. EVs can act as regulators of normal homeostasis, but they can also promote either neuroinflammation/degeneration or tissue repair in pathological conditions, depending on their content. Since EV molecular cargo constitutes a representation of the origin cell status, EVs can be exploited in the diagnosis of several diseases. Due to their capability to cross the blood–brain barrier (BBB), EVs not only have been suggested for the diagnosis of central nervous system disorders by means of minimally invasive procedures, i.e., “liquid biopsies”, but they are also considered attractive tools for targeted drug delivery across the BBB. From the therapeutic perspective, mesenchymal stem cells (MSCs) represent one of the most promising sources of EVs. In particular, the neuroprotective properties of MSCs derived from the dental pulp are here discussed.

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“…Multi-dose stem cell transplantation through the IN route may help to prolong the duration of the therapeutic effect, though there is no report on the use of IN for the administration of pluripotent stem cells. Besides pluripotent stem cells, researches showed that weekly IN administration of MSCs or EVs could reduce neuron loss and improve rat behavioral performance 156 , 157 , 158 . These reports support the feasibility of repeated IN administration of stem cells for PD treatment.…”

Section: Benefits Of Combining Stem Cells or Evs-based Therapy With I...mentioning

confidence: 99%

New idea to promote the clinical applications of stem cells or their extracellular vesicles in central nervous system disorders: Combining with intranasal delivery

Jiang

et al. 2022

Acta Pharmaceutica Sinica B

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Time-Dependent Memory and Gait Improvement by Intranasally-Administered Extracellular Vesicles in Parkinson’s Disease Model Rats

Cited by 13 publications

References 22 publications

Intranasal Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles for the Treatment of Neurological Diseases

Intranasal Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles for the Treatment of Neurological Diseases

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

New idea to promote the clinical applications of stem cells or their extracellular vesicles in central nervous system disorders: Combining with intranasal delivery

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