Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score

Shamili, Fazileh Hosseini; Alibolandi, Mona; Rafatpanah, Houshang; Abnous, Khalil; Mahmoudi, Mahmoud; Kalantari, Mahmoud Reza; Taghdisi, Seyed Mohammad; Ramezani, Mohammad

doi:10.1016/j.jconrel.2019.02.032

Cited by 110 publications

(67 citation statements)

References 37 publications

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“…In this study, the balance of M1/M2 in EAE rates significantly deviated toward M2 phenotype and their cytokines profile (IL-10 and TGF-β), while frequency and activity of M1 cells were decreased. Interestingly for the first time, Hosseini Shamili et al (76) bioconjugated the MSC-derived exosomes to an aptamer which targets oligodendrocyte markers. The armed exosome improved proliferation of oligodendroglia cell line (OLN93) in vitro and reduced both inflammatory responses and demyelinated lesions in the CNS of EAE mice.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Ace Card to Address Autoimmune Diseases

Baharlooi

Azimi

Salehi

et al. 2020

IJSC

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With the development of novel treatments for autoimmune disorders, it has become a popular research focus which mesenchymal stem cells (MSCs) have the capacity to counteract with autoimmune diseases progression. One of the underlying mechanisms behind their activities is the release of extracellular vesicles especially exosomes. MSC-derived exosomes are hypoimmunogenic nanocarriers which contain numerous immunoregulatory factors and similar to other exosomes, are able to pass through boundaries like the blood-brain barrier (BBB). Accumulating evidence provided by animal studies has demonstrated that MSC-derived exosomes, as a novel therapy, can re-induce self-tolerance, without subsequent complications reported for other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases. Here, we briefly describe the biological characteristics of MSC-derived exosomes and review the experimentally verified outcomes for autoimmune disease therapy purposes.

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Section: Multiple Sclerosismentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Ace Card to Address Autoimmune Diseases

Baharlooi

Azimi

Salehi

et al. 2020

IJSC

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“…Nevertheless, miRNAs are not the only molecular agents that can be inserted into MSC-derived exosomes. LJM-3064 aptamer combined with MSC-derived exosomes were shown to reduce the areas of demyelination and ameliorate disease severity in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS [ 99 ]. Both enkephalin and pigment epithelium-derived factor (PEDF) were loaded into exosomes and introduced into an MCAo rat model of focal stroke, resulting in improved brain neuron density and neurological score [ 100 ]; and a reduction in infarct volume and neuronal apoptosis [ 101 ], respectively.…”

Section: Toward Msc-derived Exosome-based Therapiesmentioning

confidence: 99%

“…Insertion of molecular agents into exosomes can be accomplished by a variety of methods, either directly into the exosomes, or into the cells from which the exosomes are derived. Direct methods include chemical reactions [ 94 , 99 , 102 , 104 ], electroporation [ 100 ], cholesterol-conjugation (hydrophobic reaction) [ 94 , 98 ], and incubation [ 102 ]. Indirect methods targeting the cells include transfection (via lipofectamine or virus infection) [ 89 , 91 , 92 , 95 , 96 , 97 , 101 ], electroporation [ 106 ], or addition as a media supplement [ 103 , 105 ].…”

Section: Toward Msc-derived Exosome-based Therapiesmentioning

confidence: 99%

Promising Opportunities for Treating Neurodegenerative Diseases with Mesenchymal Stem Cell-Derived Exosomes

Guy

Offen

2020

Biomolecules

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Neurodegenerative disease refers to any pathological condition in which there is a progressive decline in neuronal function resulting from brain atrophy. Despite the immense efforts invested over recent decades in developing treatments for neurodegenerative diseases, effective therapy for these conditions is still an unmet need. One of the promising options for promoting brain recovery and regeneration is mesenchymal stem cell (MSC) transplantation. The therapeutic effect of MSCs is thought to be mediated by their secretome, and specifically, by their exosomes. Research shows that MSC-derived exosomes retain some of the characteristics of their parent MSCs, such as immune system modulation, regulation of neurite outgrowth, promotion of angiogenesis, and the ability to repair damaged tissue. Here, we summarize the functional outcomes observed in animal models of neurodegenerative diseases following MSC-derived exosome treatment. We will examine the proposed mechanisms of action through which MSC-derived exosomes mediate their therapeutic effects and review advanced studies that attempt to enhance the improvement achieved using MSC-derived exosome treatment, with a view towards future clinical use.

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“…Engineered EVs emerged also as a great potential nano-therapeutic tool. MSC exosomes armed with high affinity aptamer toward myelin were administrated to EAE model and produced a robust suppression of inflammatory response as well as lowered demyelination lesion region in CNS, resulting in reduced severity of EAE disease [ 102 ]. Mokarizadeh and colleagues addressed in vitro the potentiality of exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells, when incubated with EAE mice splenic lymphocytes.…”

Section: New Therapeutic Perspectivesmentioning

confidence: 99%

Emerging Role of Extracellular Vesicles in the Pathophysiology of Multiple Sclerosis

Dolcetti

Bruno

Guadalupi

et al. 2020

IJMS

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Extracellular vesicles (EVs) represent a new reality for many physiological and pathological functions as an alternative mode of intercellular communication. This is due to their capacity to interact with distant recipient cells, usually involving delivery of the EVs contents into the target cells. Intensive investigation has targeted the role of EVs in different pathological conditions, including multiple sclerosis (MS). MS is a chronic inflammatory and neurodegenerative disease of the nervous system, one of the main causes of neurological disability in young adults. The fine interplay between the immune and nervous systems is profoundly altered in this disease, and EVs seems to have a relevant impact on MS pathogenesis. Here, we provide an overview of both clinical and preclinical studies showing that EVs released from blood–brain barrier (BBB) endothelial cells, platelets, leukocytes, myeloid cells, astrocytes, and oligodendrocytes are involved in the pathogenesis of MS and of its rodent model experimental autoimmune encephalomyelitis (EAE). Most of the information points to an impact of EVs on BBB damage, on spreading pro-inflammatory signals, and altering neuronal functions, but EVs reparative function of brain damage deserves attention. Finally, we will describe recent advances about EVs as potential therapeutic targets and tools for therapeutic intervention in MS.

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Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score

Cited by 110 publications

References 37 publications

Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Ace Card to Address Autoimmune Diseases

Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Ace Card to Address Autoimmune Diseases

Promising Opportunities for Treating Neurodegenerative Diseases with Mesenchymal Stem Cell-Derived Exosomes

Emerging Role of Extracellular Vesicles in the Pathophysiology of Multiple Sclerosis

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