Potential of Exosomes for the Treatment of Stroke

Stroke is the result of blockage or rupture of blood vessels in the brain and is the leading cause of death and disability in the world. Currently only a very limited number of therapeutic approaches are available for treatment of stroke patients, and the vast majority of neuroprotective agents that tested positively in pre-clinical studies failed in clinical trials. In recent years, the clinical value of the use of exosomes for stroke treatment has received widespread attention due their unique characteristics such as low immunogenicity, low toxicity and biodegradability, ability to cross the blood–brain barrier (BBB), and their important role in communication between cells. More and more evidence suggests that the secretion of exosomes is the mechanism underlying the protection induced by mesenchymal stromal cells (MSCs) after stroke. Exosomes are thought to support brain restoration and induce repairing effects, including neurovascular remodeling, and anti-apoptosis and anti-inflammatory effects. Recent reports have focused on the clinical application of exosomes as a potential drug delivery approach. This review focuses on the ability of exosomes to interrupt the stroke-induced pathologic processes of stroke, and on publications describing how to achieve more effective treatment of stroke with exosomes.

Download Full-text

Potential Role of Exosomes in Ischemic Stroke Treatment

Biomolecules ◽

10.3390/biom12010115 ◽

2022 ◽

Vol 12 (1) ◽

pp. 115

Author(s):

Lingling Jiang ◽

Weiqi Chen ◽

Jinyi Ye ◽

Yilong Wang

Keyword(s):

Ischemic Stroke ◽

Positive Impact ◽

Current Knowledge ◽

Therapeutic Effects ◽

Stroke Treatment ◽

Neuroprotective Drugs ◽

Life Threatening ◽

Low Toxicity ◽

Neurovascular Remodeling

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.

Download Full-text

Lessons From the Neural Bases of Speech and Voice

Perspectives on Speech Science and Orofacial Disorders ◽

10.1044/ssod21.1.5 ◽

2011 ◽

Vol 21 (1) ◽

pp. 5-14

Author(s):

Christy L. Ludlow

Keyword(s):

Brain Networks ◽

Neural Substrates ◽

Voice Behavior ◽

Therapeutic Approaches ◽

Neural Bases ◽

Sound Foundation ◽

The Brain ◽

Normal Speech

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.

Download Full-text

Reflex Epilepsy with Hot Water: Clinical and EEG Findings, Treatment, and Prognosis in Childhood

Neuropediatrics ◽

10.1055/s-0040-1709455 ◽

2020 ◽

Vol 51 (05) ◽

pp. 336-340 ◽

Cited By ~ 1

Author(s):

Fatma Hanci ◽

Sevim Türay ◽

Paşa Balci ◽

Nimet Kabakuş

Keyword(s):

Seizure Control ◽

Hot Water ◽

Reflex Epilepsy ◽

Therapeutic Approaches ◽

Water Age ◽

Epileptiform Discharges ◽

Neurology Clinic ◽

Neuromuscular Development ◽

The Brain ◽

International League

AbstractHot water epilepsy (HWE) is a subtype of reflex epilepsy in which seizures are triggered by the head being immersed in hot water. Hot water or bathing epilepsy is the type of reflex epilepsy most frequently encountered in our clinic. We describe our patients with HWE and also discuss the clinical features, therapeutic approaches, and prognosis. Eleven patients (10 boys, 1 girl), aged 12 months to 13 years, admitted to the pediatric neurology clinic between January 2018 and August 2019, and diagnosed with HWE or bathing epilepsy based on International League Against Epilepsy (ILAE)-2017, were followed up prospectively for ∼18 months. Patients' clinical and electroencephalography (EEG) findings and treatment details were noted. All 11 patients' seizures were triggered by hot water. Age at first seizure was between 2 months and 12 years. Seizure types were generalized motor seizures, absence, and atonic. EEG was normal in two patients, but nine patients had epileptiform discharges. Magnetic resonance imaging of the brain was performed and reported as normal (except in one case). Histories of prematurity were present in two patients, unprovoked seizures in one, and low birth weight and depressed birth in the other. Patients with HWE have normal neuromuscular development and neurological examination results, together with prophylaxis or seizure control with a single antiepileptic drug, suggesting that it is a self-limited reflex epilepsy.

Download Full-text

Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Cells ◽

10.3390/cells10040767 ◽

2021 ◽

Vol 10 (4) ◽

pp. 767

Author(s):

Courtney Davis ◽

Sean I. Savitz ◽

Nikunj Satani

Keyword(s):

Ischemic Stroke ◽

Extracellular Vesicles ◽

Neurovascular Unit ◽

Culture Conditions ◽

Therapeutic Effects ◽

Stroke Treatment ◽

Inflammatory Molecules ◽

The Brain

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

Download Full-text

Chronic Inflammation and Radiation-Induced Cystitis: Molecular Background and Therapeutic Perspectives

Cells ◽

10.3390/cells10010021 ◽

2020 ◽

Vol 10 (1) ◽

pp. 21

Author(s):

Carole Helissey ◽

Sophie Cavallero ◽

Clément Brossard ◽

Marie Dusaud ◽

Cyrus Chargari ◽

...

Keyword(s):

Stromal Cells ◽

Therapeutic Strategy ◽

Randomized Trials ◽

Clinical Presentation ◽

Therapeutic Approaches ◽

Radiation Cystitis ◽

Fibrotic Process ◽

Radiation Induced ◽

Therapeutic Irradiation ◽

Underlying Pathophysiology

Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers. Its clinical management remains unclear, and few preclinical data are available on its underlying pathophysiology. The therapeutic strategy is difficult to establish because few prospective and randomized trials are available. In this review, we report on the clinical presentation and pathophysiology of radiation cystitis. Then we discuss potential therapeutic approaches, with a focus on the immunopathological processes underlying the onset of radiation cystitis, including the fibrotic process. Potential therapeutic avenues for therapeutic modulation will be highlighted, with a focus on the interaction between mesenchymal stromal cells and macrophages for the prevention and treatment of radiation cystitis.

Download Full-text

Metabolism in the Zebrafish Retina

Journal of Developmental Biology ◽

10.3390/jdb9010010 ◽

2021 ◽

Vol 9 (1) ◽

pp. 10

Author(s):

Natalia Jaroszynska ◽

Philippa Harding ◽

Mariya Moosajee

Keyword(s):

Pigment Epithelium ◽

Retinal Pigment ◽

The Body ◽

Therapeutic Approaches ◽

Retinal Photoreceptors ◽

Sufficient Energy ◽

Metabolic Products ◽

Sight Loss ◽

Choroidal Vasculature ◽

The Brain

Retinal photoreceptors are amongst the most metabolically active cells in the body, consuming more glucose as a metabolic substrate than even the brain. This ensures that there is sufficient energy to establish and maintain photoreceptor functions during and after their differentiation. Such high dependence on glucose metabolism is conserved across vertebrates, including zebrafish from early larval through to adult retinal stages. As the zebrafish retina develops rapidly, reaching an adult-like structure by 72 hours post fertilisation, zebrafish larvae can be used to study metabolism not only during retinogenesis, but also in functionally mature retinae. The interplay between rod and cone photoreceptors and the neighbouring retinal pigment epithelium (RPE) cells establishes a metabolic ecosystem that provides essential control of their individual functions, overall maintaining healthy vision. The RPE facilitates efficient supply of glucose from the choroidal vasculature to the photoreceptors, which produce metabolic products that in turn fuel RPE metabolism. Many inherited retinal diseases (IRDs) result in photoreceptor degeneration, either directly arising from photoreceptor-specific mutations or secondary to RPE loss, leading to sight loss. Evidence from a number of vertebrate studies suggests that the imbalance of the metabolic ecosystem in the outer retina contributes to metabolic failure and disease pathogenesis. The use of larval zebrafish mutants with disease-specific mutations that mirror those seen in human patients allows us to uncover mechanisms of such dysregulation and disease pathology with progression from embryonic to adult stages, as well as providing a means of testing novel therapeutic approaches.

Download Full-text

Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study

Molecules ◽

10.3390/molecules26061616 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1616

Author(s):

Nicoletta di Leo ◽

Stefania Moscato ◽

Marco Borso' ◽

Simona Sestito ◽

Beatrice Polini ◽

...

Keyword(s):

High Performance ◽

In Vitro Model ◽

New Drugs ◽

Therapeutic Approaches ◽

Neuroprotective Effects ◽

Pharmacological Response ◽

Preliminary Study ◽

Vitro Model ◽

The Brain

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

Download Full-text

Redirecting adult mesenchymal stromal cells to the brain: a new approach for treating CNS autoimmunity and neuroinflammation?

Immunology and Cell Biology ◽

10.1111/imcb.12014 ◽

2018 ◽

Vol 96 (4) ◽

pp. 347-357

Author(s):

Jasmine J Wilson ◽

Kerrie L Foyle ◽

Jade Foeng ◽

Todd Norton ◽

Duncan R McKenzie ◽

...

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

New Approach ◽

Cns Autoimmunity ◽

The Brain

Download Full-text

Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo-Is Immunosuppression Mandatory?

Cells ◽

10.3390/cells10071804 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1804

Author(s):

Urszula Kozlowska ◽

Aleksandra Klimczak ◽

Karolina Anna Bednarowicz ◽

Tomasz Zalewski ◽

Natalia Rozwadowska ◽

...

Keyword(s):

Immune Reaction ◽

Disease Model ◽

Immunosuppressive Drugs ◽

Therapeutic Approaches ◽

Stem Cell Graft ◽

Skeletal Muscle Loss ◽

The Brain ◽

Privileged Site ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study aimed to research the efficiency of glial restricted progenitors (GRPs) grafted into murine CNS (central nervous system) in healthy models and the SOD1G93A ALS disease model. The cellular grafts were administered in semiallogenic and allogeneic settings. To investigate the models of immune reaction against grafted GRPs, we applied three immunosuppressive/immunomodulatory regimens: preimplantation factor (PiF); Tacrolimus; and CTLA-4, MR1 co-stimulatory blockade. We tracked the cells with bioluminescence imaging (BLI) in vivo to study their survival. The immune response character was evaluated with brain tissue assays and multiplex ELISA in serum and cerebrospinal fluid (CSF). The application of immunosuppressive drugs is disputable when considering cellular transplants into the immune-privileged site/brain. However, our data revealed that semiallogenic GRP graft might survive inside murine CNS without the necessity to apply any immunomodulation or immunosuppression, whereas, in the situation of allogeneic mouse setting, the combination of CTLA-4, MR1 blockade can be considered as the best immunosuppressive option.

Download Full-text

Mesenchymal Stromal Cell Secretome for the Treatment of Immune-Mediated Inflammatory Diseases: Latest Trends in Isolation, Content Optimization and Delivery Avenues

Pharmaceutics ◽

10.3390/pharmaceutics13111802 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1802

Author(s):

Elena Munoz-Perez ◽

Ainhoa Gonzalez-Pujana ◽

Manoli Igartua ◽

Edorta Santos-Vizcaino ◽

Rosa Maria Hernandez

Keyword(s):

Stromal Cells ◽

State Of The Art ◽

Inflammatory Diseases ◽

Therapeutic Approaches ◽

Pharmacological Management ◽

Beneficial Effects ◽

New Therapeutic Approaches ◽

Immune Mediated ◽

High Prevalence ◽

Inflammatory Processes

Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.

Download Full-text