Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice

Perets, Nisim; Hertz, Stav; London, Michael; Offen, Daniel

doi:10.1186/s13229-018-0240-6

Cited by 137 publications

(146 citation statements)

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“…Indeed, using the same BTBR model, we were able to show that intranasal administration of human MSCs derived exosomes (MSC-exo) resulted in significant improvement in the core symptoms including social interaction, ultrasonic communication, and repetitive behaviors 13 . Furthermore, we have demonstrated that MSC-derived exosomes migrate to specific neuropathological locations in rodent models for stroke, Parkinson's Disease Alzheimer's Disease, spinal cord injury and ASD.…”

Section: Introductionmentioning

confidence: 93%

“…Reciprocal dyadic social interaction test. The reciprocal dyadic social interaction test was done as previously described [32][33][34] . Prior to the test, each mouse was separated for social isolation of 1-2 hours.…”

Section: Behavioral Testsmentioning

confidence: 99%

“…Ultrasonic vocalizations. The ultrasonic vocalization test was done as previously described 32,34 . Both Shank3B KO and WT males met WT females, all sexually naive.…”

Section: -Chambered Social Interaction Testmentioning

confidence: 99%

“…Exosomes were isolated and characterized as previously described 14,34,36 . Purification of exosomes 6 was done using differential centrifugation protocol.…”

Section: Exosomes Purification Protocolmentioning

confidence: 99%

“…The pellet containing the purified exosomes was re-suspended in 200 µm of sterilized PBS. MSC-exo were characterized using Nanosight technology, TEM, western blotting as previously described 14,15,34 .…”

Section: Exosomes Purification Protocolmentioning

confidence: 99%

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Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mice model of autism Shank3B

Perets

Oron

Herman

et al. 2020

Preprint

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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with main core symptoms including deficits in social-communication abilities and repetitive behaviors/restricted interests. ASD affects 1 of 88 children worldwide and currently there is no sufficiently effective treatment that alleviates its core deficits. In our previous studies, we have shown that both MSC and MSC-exo can ameliorate core ASD-like symptoms of the BTBR multifactorial mouse model of autism. Furthermore, we have demonstrated that the MSC-exo migrate to distinct neuropathological areas in several mouse models, including the frontal cortex and cerebellum in BTBR mice. In contrast to BTBR mice, which is a multifactorial model of autism, the Shank3B KO mouse is used to study ASD which develops due to a specific genetic mutation. Here we demonstrate that intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization and reduces repetitive behaviors. We also observed an increase of GABRB1 in the prefrontal cortex. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of in this mouse model autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.

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Section: Introductionmentioning

confidence: 93%

Section: Behavioral Testsmentioning

confidence: 99%

“…Ultrasonic vocalizations. The ultrasonic vocalization test was done as previously described 32,34 . Both Shank3B KO and WT males met WT females, all sexually naive.…”

Section: -Chambered Social Interaction Testmentioning

confidence: 99%

“…Exosomes were isolated and characterized as previously described 14,34,36 . Purification of exosomes 6 was done using differential centrifugation protocol.…”

Section: Exosomes Purification Protocolmentioning

confidence: 99%

Section: Exosomes Purification Protocolmentioning

confidence: 99%

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Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mice model of autism Shank3B

Perets

Oron

Herman

et al. 2020

Preprint

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Intranasal Delivery of Functionalized Polymeric Nanomaterials to the Brain

Zha

Wong

All

2022

Adv Healthcare Materials

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Intravenous delivery of nanomaterials containing therapeutic agents and various cargos for treating neurological disorders is often constrained by low delivery efficacy due to difficulties in passing the blood-brain barrier (BBB). Nanoparticles (NPs) administered intranasally can move along olfactory and trigeminal nerves so that they do not need to pass through the BBB, allowing non-invasive, direct access to selective neural pathways within the brain. Hence, intranasal (IN) administration of NPs can effectively deliver drugs and genes into targeted regions of the brain, holding potential for efficacious disease treatment in the central nervous system (CNS). In this review, current methods for delivering conjugated NPs to the brain are primarily discussed. Distinctive potential mechanisms of therapeutic nanocomposites delivered via IN pathways to the brain are then discussed. Recent progress in developing functional NPs for applications in multimodal bioimaging, drug delivery, diagnostics, and therapeutics is also reviewed. This review is then concluded by discussing existing challenges, new directions, and future perspectives in IN delivery of nanomaterials.

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Emerging Prospects of Exosomes for Cancer Treatment: From Conventional Therapy to Immunotherapy

et al. 2020

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remains unclear how and why cancer occurs and progresses. Using an evolutionary approach, the concept of a complex adaptive system (CAS) was developed to describe the behaviors of cancer tumorigenesis, [2] which may suggest a frameshift away from the limitations of current approaches that mainly address the importance of alteration in specific target molecules in cancer cells. This change in perspectives toward tumors, not simply as a disease to be cured but also as CAS, is expected to be the cornerstone of the paradigm shift toward innovative cancer therapies. [3] The human immune system can also be viewed as a CAS and therefore expected to initiate self-defense mechanisms against cancer in a complex adaptive manner as long as it recognizes the cancer cells as the non-self-signals. Consequently, the key to controlling cancer could lie in understanding how to manipulate the immune system and strengthen its defenses against cancer. The concept of facilitating the immune system to fight against cancer was first suggested in the late 1800s by Dr. Wiliam Coley, who was the first to observe anti-tumor effects after intratumoral injection of microbe-derived toxins. [4] Since then, the field of cancer immunotherapy research has flourished, resulting in clinical achievements such as immune checkpoint blockades and chimeric antigen receptor T cell (CAR-T) therapy. [5] However, immune suppression resistance mechanisms have simultaneously been identified that have impeded favorable response to cancer immunotherapy. [6,7] Exosome-based cancer therapies have emerged as a potential option for overcoming these limitations to the effects of current cancer therapies due to their pathophysiological efficacy against tumors. [8] Exosomes are secreted externally by cells and are found ubiquitously in blood, urine, saliva, cerebrospinal fluid, pleural fluid, and breast milk. [9,10] The distinction between different types of extracellular vesicles (EVs) is unclear; however, they are conventionally classified as either ectosomes (microvesicles or microparticles) or exosomes. [11] While ectosomes are formed by the outward budding of the plasma membrane, exosomes are formed from multivesicular bodies (MVB) containing intraluminal vesicles via inward budding of the late endosome, which later fuses to the membrane. The formed vesicles are then secreted via a process known as exocytosis (Figure 1). The two types of vesicle also differ in diameter, Exosomes are a class of extracellular vesicles of around 100 nm in diameter that are secreted by most cells and contain various bioactive molecules reflecting their cellular origin and mediate intercellular communication. Studies of these exosomal features in tumor pathogenesis have led to the development of therapeutic and diagnostic approaches using exosomes for cancer therapy. Exosomes have many advantages for conveying therapeutic agents such as small interfering RNAs, microRNAs, membrane-associated proteins, and chemotherapeutic compounds; thus, they are considered a prime candidate as a deliv...

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Intranasal administration of exosomes derived from mesenchymal stem cells ameliorates autistic-like behaviors of BTBR mice

Cited by 137 publications

References 50 publications

Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mice model of autism Shank3B

Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mice model of autism Shank3B

Intranasal Delivery of Functionalized Polymeric Nanomaterials to the Brain

Emerging Prospects of Exosomes for Cancer Treatment: From Conventional Therapy to Immunotherapy

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