Stem cell therapies for neurological disorders: current progress, challenges, and future perspectives

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: July 25, 2024

Stem cell-based therapies have emerged as a promising approach for treating various neurological disorders by harnessing the regenerative potential of stem cells to restore damaged neural tissue and circuitry. This comprehensive review provides an in-depth analysis current state cell applications in primary conditions, including Parkinson's disease (PD), Alzheimer's (AD), amyotrophic lateral sclerosis (ALS), multiple (MS), stroke, spinal cord injury (SCI), other related disorders. The begins with detailed introduction biology, discussing types, sources, mechanisms action therapies. It then critically examines preclinical evidence from animal models early human trials investigating safety, feasibility, efficacy different such embryonic (ESCs), mesenchymal (MSCs), (NSCs), induced pluripotent (iPSCs). While ESCs been studied extensively models, clinical primarily focused on adult MSCs NSCs, well iPSCs their derivatives. We assess research each type, highlighting limitations conditions. synthesizes key findings recent, high-quality studies condition, manufacturing, delivery methods, therapeutic outcomes. replace lost neurons directly reconstruct circuits is highlighted, emphasizes critical role paracrine immunomodulatory mediating effects most article also explores challenges associated translating into practice, issues sourcing, scalability, regulatory considerations. Furthermore, it discusses future directions opportunities advancing treatments, gene editing, biomaterials, personalized iPSC-derived therapies, novel strategies. concludes emphasizing transformative revolutionizing treatment while acknowledging need rigorous trials, standardized protocols, multidisciplinary collaboration realize full promise.

Language: Английский

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Oligodendrocyte precursor cells: the multitaskers in the brain

Pflügers Archiv - European Journal of Physiology, Journal Year: 2023, Volume and Issue: 475(9), P. 1035 - 1044

Published: July 4, 2023

Abstract In the central nervous system, oligodendrocyte precursor cells (OPCs) are recognized as progenitors responsible for generation of oligodendrocytes, which play a critical role in myelination. Extensive research has shed light on mechanisms underlying OPC proliferation and differentiation into mature myelin-forming oligodendrocytes. However, recent advances field have revealed that OPCs multiple functions beyond their progenitors, exerting control over neural circuits brain function through distinct pathways. This review aims to provide comprehensive understanding by first introducing well-established features. Subsequently, we delve emerging roles modulating both healthy diseased states. Unraveling cellular molecular influence holds great promise identifying novel therapeutic targets system diseases.

Language: Английский

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Cerebrospinal fluid of progressive multiple sclerosis patients reduces differentiation and immune functions of oligodendrocyte progenitor cells

Glia, Journal Year: 2022, Volume and Issue: 70(6), P. 1191 - 1209

Published: March 9, 2022

Oligodendrocyte progenitor cells (OPCs) are responsible for remyelination in the central nervous system (CNS) health and disease. For patients with multiple sclerosis (MS), is not always successful, mechanisms differentiating successful from failed well-known. Growing evidence suggests an immune role OPCs, addition to their regenerative role; however, it clear if this helps or hinders process. We studied effect of cerebrospinal fluid (CSF) relapsing MS (rMS) progressive (pMS) on primary OPC differentiation gene expression function. observed that CSF either rMS pMS has a differential ability mice OPCs differentiate into mature oligodendrocytes express functions. impaired oligodendrocytes. In addition, led decreased major histocompatibility complex class (MHC)-II expression, tumor necrosis factor (TNF)-α secretion, nuclear kappa-B (NFκB) activation, less activation proliferation T cells. Our findings suggest only remyelination, but they may also play active as innate CNS.

Language: Английский

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Anti‐ and pro‐inflammatory milieu differentially regulate differentiation and immune functions of oligodendrocyte progenitor cells

Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 19, 2024

Oligodendrocyte progenitor cells (OPCs) were regarded for years solely their regenerative role; however, immune-modulatory roles have gained much attention recently, particularly in the context of multiple sclerosis (MS). Despite extensive studies on OPCs, there are limited data elucidating interactions between intrinsic and immune functions, as well relationship with inflamed central nervous system (CNS) environment, a key factor MS pathology. We examined effects pro-inflammatory cytokines, represented by interferon (IFN)-γ tumour necrosis (TNF)-α, anti-inflammatory interleukin (IL)-4 IL-10, OPC differentiation characteristics. Using primary cultures, enzyme-linked immunosorbent assay immunofluorescence stainings, we assessed capacity, phagocytic activity, major histocompatibility complex (MHC)-II expression, cytokine secretion. observed that milieu (IL4 IL10) reduced both functions. Conversely, exposure to TNF-α led intact differentiation, increased high levels MHC-II cytokines Those attributed signalling via TNF-receptor-2 counteracted detrimental IFN-γ differentiation. Our findings suggest pro-regenerative, permissive inflammatory environment is needed OPCs execute

Language: Английский

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The interplay of inflammation and remyelination: rethinking MS treatment with a focus on oligodendrocyte progenitor cells

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: July 12, 2024

Multiple sclerosis (MS) therapeutic goals have traditionally been dichotomized into two distinct avenues: immune-modulatory-centric interventions and pro-regenerative strategies. Oligodendrocyte progenitor cells (OPCs) were regarded for many years solely in concern to their potential generate oligodendrocytes myelin the central nervous system (CNS). However, accumulating data elucidate multifaceted roles of OPCs, including immunomodulatory functions, positioning them as cardinal constituents CNS's immune landscape.

Language: Английский

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Cerebrospinal fluid immunoglobulins in primary progressive multiple sclerosis are pathogenic

Brain, Journal Year: 2023, Volume and Issue: 146(5), P. 1979 - 1992

Published: Feb. 3, 2023

Abstract Multiple sclerosis is clinically characterized by relapses and remissions (relapsing-remitting multiple sclerosis) that over time may evolve to a progressive course (secondary or as having from disease onset (primary sclerosis). At present, it not definitively known whether these clinical entities constitute single pathological manifestations represent two distinct sharing inflammatory demyelination feature. Here we show using novel mouse model CSF of primary patients unique in its capacity induce motor disability spinal cord pathology including demyelination, impaired remyelination, reactive astrogliosis axonal damage. Notably, removal immunoglobulin G via filtration immunodepletion attenuates pathogenic capacity. Furthermore, injection recombinant antibodies derived recapitulates the pathology. Our findings suggest features are antibody-mediated pathogenically relapsing-remitting secondary sclerosis. study has potentially important implications for development specific therapies with

Language: Английский

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The Role of Oligodendrocyte Lineage Cells in the Pathogenesis of Alzheimer’s Disease

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(1)

Published: Jan. 3, 2025

Language: Английский

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The Percentage of Neutrophils is Independently Associated with Blood-Brain Barrier(BBB) Disruption in Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease (MOGAD)

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2823 - 2836

Published: Feb. 1, 2025

This study aims to investigate the risk factors associated with blood-brain barrier(BBB) disruption in patients myelin oligodendrocyte glycoprotein antibody disease(MOGAD). We collected clinical data from 95 diagnosed MOGAD at Department of Neurology, First Affiliated Hospital Zhengzhou University October 2018 May 2024. Patients were classified into normal or damaged BBB groups based on cerebrospinal fluid (CSF) albumin/serum albumin (QAlb). Binary logistic regression analysis was used evaluate for patients. Our revealed that damaged, there is a higher proportion acute phase high EDSS scores, incidence prodromal symptoms, and rate viral infections. Myelitis main phenotype, manifestations primarily including limb weakness bladder/bowel dysfunction. Laboratory tests showed levels CSF protein, immunoglobulin (IgG), 24-hour intrathecal IgG synthesis rate, peripheral blood leukocytes, neutrophil percentage, NLR, anti-thyroglobulin antibodies(TGAbs), fibrinogen levels, while free triiodothyronine (FT3) lymphocyte percentage lower. Multivariate indicated an increased independent factor damage (OR=1.068, 95% CI: 1.018-1.122, P=0.008). Neutrophil readily available widely indicator reflecting immune system's state body's inflammation level. The change independently finding helps provide more reference information personalized treatment decisions further research pathogenesis MOGAD.

Language: Английский

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Role of Oligodendrocyte Lineage Cells in Multiple System Atrophy

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 739 - 739

Published: Feb. 25, 2023

Multiple system atrophy (MSA) is a debilitating movement disorder with unknown etiology. Patients present characteristic parkinsonism and/or cerebellar dysfunction in the clinical phase, resulting from progressive deterioration nigrostriatal and olivopontocerebellar regions. MSA patients have prodromal phase subsequent to insidious onset of neuropathology. Therefore, understanding early pathological events important determining pathogenesis, which will assist developing disease-modifying therapy. Although definite diagnosis relies on positive post-mortem finding oligodendroglial inclusions composed α-synuclein, only recently has been verified as an oligodendrogliopathy secondary neuronal degeneration. We review up-to-date knowledge human oligodendrocyte lineage cells their association discuss postulated mechanisms how develops, progenitor potential origins toxic seeds possible networks through induces loss. Our insights shed new light research directions for future studies.

Language: Английский

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Disease-associated oligodendroglia: a putative nexus in neurodegeneration

Trends in Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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