Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(4), P. 1207 - 1216

Published: April 3, 2024

Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, neuromuscular junction. In amyotrophic lateral sclerosis, where neuron is progressively lost, cell may also be impaired. Recently, important signaling potential trophic activities cell-derived exosomal vesicles have been reported. This case report describes treatment a patient with advanced sclerosis using serial intravenous infusions allogeneic vesicles, marking, to our knowledge, first instance such treatment. An 81-year-old male presented 1.5-year history rapidly progressive sclerosis. After initial diagnosis, underwent combination generic riluzole, sodium phenylbutyrate taurursodiol. The volunteered participate in an FDA-approved single-patient expanded access received weekly potentially restore impaired function. We confirmed that cultured obtained from via sural nerve biopsy appeared (senescent) exposure patient’s cadaver donor improved their growth capacity vitro. period observation lasting 10 weeks, during which Functional Rating Scale-Revised pulmonary were regularly monitored, consecutive 1.54 × 12 (×2), then 7.5 (×6) diluted 40 mL Dulbecco’s phosphate-buffered saline. None associated adverse events as infusion reactions (allergic or otherwise) changes vital signs. Clinical lab serum neurofilament cytokine levels measured prior each varied somewhat without clear trend. A more sensitive in-house assay suggested possible inflammasome activation disease course. trend clinical stabilization was observed period. Our study provides novel approach address possibly patients vesicles. Initial findings suggest this safe.

Language: Английский

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Stem Cell-Derived Extracellular Vesicle-Mediated Therapeutic Signaling in Spinal Cord Injury

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 723 - 723

Published: Jan. 16, 2025

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized possess unique properties such low immunogenicity and the ability to cross biological barriers, making them ideal carriers delivering bioactive molecules injured tissues. MSC-EVs been demonstrated exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, enhancing axonal regeneration. Recent studies delved into molecular mechanisms underlying MSC-EV-mediated effects. Exosomal microRNAs (miRNAs) identified key regulators of various cellular processes involved SCI pathogenesis repair. miRNAs can influence oxidative stress, apoptosis by modulating gene expression. This review summarized current state MSC-EV-based therapies highlighting potential clinical applications. We discussed challenges limitations translating these practice, inconsistent EV production, complex cargo composition, need targeted delivery strategies. Future research should focus on optimizing production characterization, identifying miRNAs, developing innovative systems maximize SCI.

Language: Английский

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Nanoparticle Strategies for Treating CNS Disorders: A Comprehensive Review of Drug Delivery and Theranostic Applications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13302 - 13302

Published: Dec. 11, 2024

This review aims to address the significant challenges of treating central nervous system (CNS) disorders such as neurodegenerative diseases, strokes, spinal cord injuries, and brain tumors. These are difficult manage due complexity disease mechanisms protective blood–brain barrier (BBB), which restricts drug delivery. Recent advancements in nanoparticle (NP) technologies offer promising solutions, with potential applications delivery, neuroprotection, neuroregeneration. By examining current research, we explore how NPs can cross BBB, deliver medications directly targeted CNS regions, enhance both diagnostics treatment. Key NP strategies, passive targeting, receptor-mediated transport, stimuli-responsive systems, demonstrate encouraging results. Studies show that may improve minimize side effects, increase therapeutic effectiveness models Alzheimer’s, Parkinson’s, stroke, glioblastoma. thus represent a approach for disorder management, combining delivery diagnostic capabilities enable more precise effective treatments could significantly benefit patient outcomes.

Language: Английский

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Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury

Journal of Neurotrauma, Journal Year: 2024, Volume and Issue: 41(21-22), P. 2395 - 2412

Published: March 6, 2024

There is a growing body of evidence that the delivery cell-derived exosomes normally involved in intracellular communication can reduce secondary injury mechanisms after brain and spinal cord improve outcomes. Exosomes are nanometer-sized vesicles released by Schwann cells may have neuroprotective effects reducing posttraumatic inflammatory processes as well promoting tissue healing functional recovery. The purpose this study was to evaluate beneficial human Schwann-cell (hSC-Exos) severe model penetrating ballistic-like (PBBI) rats investigate on multiple Human cell processing protocols followed Current Good Manufacturing Practices (cGMP) with exosome extraction purification steps approved FDA for an expanded access single ALS patient IND. Anesthetized male Sprague-Dawley (280-350g) underwent PBBI surgery or sham procedures starting 30 min received either dose hSC-Exos PBS through jugular vein. At 48hrs PBBI, flow cytometry analysis cortical revealed administration reduced number activated microglia levels caspase-1, marker inflammasome activation. Neuropathological at 21 days showed treatment significantly overall contusion volume decreased frequency Iba-1 positive amoeboid immunocytochemical analysis. This systemic TBI reduces histopathological damage. represents clinically relevant cell-based therapy limit detrimental neurotrauma other progressive neurological injuries impacting pathophysiological events

Language: Английский

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The phenotypic changes of Schwann cells promote the functional repair of nerve injury

Neuropeptides, Journal Year: 2024, Volume and Issue: 106, P. 102438 - 102438

Published: May 11, 2024

Language: Английский

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Diabetic peripheral neuropathy based on Schwann cell injury: mechanisms of cell death regulation and therapeutic perspectives

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 12, 2024

Diabetic peripheral neuropathy (DPN) is a complication of diabetes mellitus that lacks specific treatment, its high prevalence and disabling neuropathic pain greatly affects patients’ physical mental health. Schwann cells (SCs) are the major glial nervous system, which play an important role in various inflammatory metabolic neuropathies by providing nutritional support, wrapping axons promoting repair regeneration. Increasingly, glucose (HG) has been found to promote progression DPN pathogenesis targeting SCs death regulation, thus revealing molecular process programmed cell (PCD) disrupted link gain insight into DPN. This paper first review recent progress HG studies on apoptosis, autophagy, pyroptosis, ferroptosis necroptosis pathways SCs, points out crosstalk between PCDs related therapeutic perspectives, with aim new perspectives for deeper understanding mechanisms exploration effective targets.

Language: Английский

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Schwann Cell-Derived Exosomes Induced Axon Growth after Spinal Cord Injury by Decreasing PTP-σ Activation on CSPGs via the Rho/ROCK Pathway

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(8), P. 2120 - 2130

Published: May 31, 2024

Language: Английский

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Comparison of cellular-based therapies following a long-segmental peripheral nerve defect in a rat model

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0313292 - e0313292

Published: Jan. 7, 2025

Peripheral nerve injury (PNI) is characterized by a loss of cellular and axonal integrity, often leading to limited functional recovery pain. Many PNIs are not amenable repair with traditional techniques; however, cell therapies, particularly Schwann cells (SCs), offer the promise neural tissue replacement improvement. Exosomes, which carry signaling molecules, can be secreted SCs have shown in PNI. Our laboratory has had success using preclinical clinical treatment settings. Transplanted several known limitations, exosomes mitigate. To that end, current study investigated if implanted SC-derived conduits, conduits SCs, reverse autograft, or empty comparably improve regeneration pain outcomes 16-weeks after long gap PNI adult rats. Results show there were no differences between groups von Frey filament testing Hargreaves test. Electrophysiological showed significant difference injured (ipsilateral) uninjured (contralateral) limbs while histological assessment counts different areas conduit. Based on results study, more research needed understand therapeutic role

Language: Английский

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Human Schwann cell exosome treatment attenuates secondary injury mechanisms, histopathological consequences, and behavioral deficits after traumatic brain injury

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00555 - e00555

Published: Feb. 1, 2025

Language: Английский

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Roles for Exosomes from Various Cellular Sources in Spinal Cord Injury

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 10, 2025

Language: Английский

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