Central Nervous System (CNS) Disorder

Exosomes have been reported to serve as a role in the treatment of many diseases including central nervous system (CNS) disorders. Due to their small size, exosomes are used as effective carriers that deliver therapeutic drugs to target cells or tissues. Besides, mesenchymal stem cells (MSCs)-derived exosomes also play an essential role in CNS diseases therapies. With the extensive experience in the field of exosome research, Creative Biolabs successfully offers a full range of exosome-related services covered from isolation to engineering for customers from all over the world. Besides, we also offer a custom service to meet our customers’ special purpose of the project.

Exosome Roles in CNS Functions

CNS is the part of the nervous system consisting of the brain and spinal cord. It combines information from the entire body and coordinates activity across the whole organism. Some studies have reported that exosomes, a type of extracellular vesicles with diameter 30~150 nm, may be involved in the CNS functions. Exosomes have been found in the cerebral spinal fluid (CSF) in both adult and embryonic animals. The presence of exosomes in the embryonic CSF suggests the possibility that they may play a role in normal brain development. Besides, the most important role of exosomes in CNS is cell-cell communication. Exosomes secreted by MSCs can transfer microRNA-133b into neurons to induce the growth of neurites. Additionally, exosome-mediated interactions between neurons and glia induce the growth of neurites and the survival of neurons. It has been reported that microRNA-124a secreted by neurons can transport into astrocytes through exosomes, thereby indirectly increasing GLT1 protein expression.

Fig.1 Postulated roles of microvesicles in neural cell communication. (Frühbeis, 2012)

Exosomes may also be involved in the pathological process of neurological disorders such as Alzheimer disease (AD), Parkinson’s disease (PD), exerting either neuro-protective or neuro-toxic functions. On one hand, exosomes mediate the removal of toxic proteins or transfer neuro-protective exosomal molecules. On the other hand, exosomes can spread potentially toxic molecules into the recipient neural cells. For example, in the AD pathological process, exosomal proteins, such as flotillins and Alix, are enriched in the amyloid plaques, suggesting exosome-associated Aβ can participate in plaque formation. It has also been reported that exosomal catalase provided a significant neuroprotective effect both in vitro and in vivo PD models.

Exosome Applications in CNS Disorders

One crucial issue in CNS disorders therapies is to transfer the therapeutic drugs to specific cell types or tissues without affecting the normal physiology of other cell types or tissues. The blood-brain barrier (BBB), however, isolates the CNS to a certain extent, creating an exclusive biochemical and immunological niche and inhibits the delivery of drugs into CNS. Hence, the delivery of drugs or therapeutic proteins to the brain is a troublesome challenge for scientists. Currently, there are a few validated non-invasive endogenous transport systems that allow therapeutic molecules to reach the CNS.

Exosome-based delivery system is an efficient delivery tool that is capable of loading with drugs and crossing the BBB via a non-invasive route. Moreover, the incorporation of drugs into exosomes increases the solubility, stability and bioavailability of the drug. Exosomes loading with siRNA against beta-site APP cleaving enzyme 1 (BACE1) were reported to transport into CNS, and individuals displayed a specific down-regulation of the BACE1 protein and relieved the symptoms of AD. Exosome-based delivery system for catalase, a potent antioxidant, was used for the PD treatment with a high drug carrying capacity and a low immunogenic profile.

Fig.2 Exosomes as drug delivery vehicles for Parkinson’s disease therapy. (Haney, 2015)

Additionally, MSCs-derived exosomes are one sort of the MSCs secretion-based paracrines characterized by without proliferation, easier preservation and transportation and less immunogenicity compared to MSCs. Studies reported that intravenous administration of MSCs-derived exosomes significantly improved functional recovery, rescued pattern separation and spatial learning impairments, promoted neurovascular remodeling (angiogenesis and neurogenesis) and reduced neuroinflammation in animal models of traumatic brain injury (TBI). Furthermore, exosomes derived from human MSC were used for stroke treatment, increasing long-term neuroprotection, promoting neuroregeneration, enhancing neurological recovery, and regulating peripheral post stroke immune responses but without effect on cerebral immune cell infiltration in mice. In addition to MSC-exosomes, exosomes from other cell types also induce neuroprotective and neurorestorative effects after stroke.

Fig.3 Exosomes help nerve tissue repair and function recovery after TBI. (Yang, 2017)

Challenges in Exosomes Therapy

The emerging role of exosomes will promote the development of therapeutic research. However, some challenges remain. First, the isolation of exosomes is complicated and expensive. Second, it is difficult to accurately find the functional molecules because exosomes include various components such as proteins, lncRNA, miRNA, and cirRNA. Third, the efficacy and safety of transgenic exosomes in vivo is still under investigation in spite of the presence of modified exosomes, especially genetically engineered exosomes. In a word, challenges remain but exosomes have an important potential in the field of disease therapy.

With the help of our advanced technologies and skillful scientists, Creative Biolabs can provide the best exosome-related services, including exosome sampling, exosome profiling, manufacture and exosome engineering. In addition, we offer customer exosome service to load interested drugs, proteins and nucleic acids into exosomes and to observe their role in disease treatment. Our high-quality service will promote your project success within a short time.

If you are interested in our services, please feel free to contact us for more details.

References:

Frühbeis, C.; et al. Emerging roles of exosomes in neuron-glia communication. Front. Physio. 2012, 3: 119.
Haney, M.J.; et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release. 2015, 207: 18-30.
Yang, Y.X.; et al. MSCs-derived exosomes and neuroinflammation, neurogenesis and therapy of traumatic brain injury. Frontiers in cellular neuroscience. 2017, 11: 55.