Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 321 - 345
Опубликована: Янв. 1, 2024
European journal of medical research, Год журнала: 2024, Номер 29(1)
Опубликована: Июль 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.
Язык: Английский
Процитировано
32
Pflügers Archiv - European Journal of Physiology, Год журнала: 2023, Номер 475(9), С. 1035 - 1044
Опубликована: Июль 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.
Язык: Английский
Процитировано
25
Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)
Опубликована: Июль 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.
Язык: Английский
Процитировано
10
Immunology, Год журнала: 2024, Номер unknown
Опубликована: Янв. 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
Язык: Английский
Процитировано
8
Neurochemical Research, Год журнала: 2025, Номер 50(1)
Опубликована: Янв. 3, 2025
Язык: Английский
Процитировано
1
Glia, Год журнала: 2022, Номер 70(6), С. 1191 - 1209
Опубликована: Март 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.
Язык: Английский
Процитировано
29
Brain, Год журнала: 2023, Номер 146(5), С. 1979 - 1992
Опубликована: Фев. 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
Язык: Английский
Процитировано
14
Cells, Год журнала: 2023, Номер 12(5), С. 739 - 739
Опубликована: Фев. 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.
Язык: Английский
Процитировано
10
Glia, Год журнала: 2024, Номер 72(9), С. 1674 - 1692
Опубликована: Июнь 20, 2024
Abstract Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this is extremely complex involves many cell types the central nervous system. In study, we have uncovered a novel function macrophage G protein‐coupled receptor kinase‐interactor 1 (GIT1) promoting remyelination functional repair after SCI. Using GIT1 flox/flox Lyz2‐Cre (GIT1 CKO) mice, identified that deficiency macrophages led to an increased generation of tumor necrosis factor‐alpha (TNFα), reduced proportion mature oligodendrocytes (mOLs), impaired remyelination, compromised recovery vivo. These effects CKO mice were reversed with administration soluble TNF inhibitor. Moreover, bone marrow transplantation from CWT adverse outcomes further indicating role modulating spinal repair. Our vitro experiments showed plays critical secreting TNFα influences differentiation oligodendrocyte precursor cells (OPCs) stimulation myelin debris. Collectively, our data new regulating transformation OPCs into mOLs, essential SCI, suggesting could be promising treatment target
Язык: Английский
Процитировано
3
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Июль 9, 2024
Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances illuminated their multifaceted nature including emerging immune functions. This review seeks to shed light on the functions exhibited by OPCs, spanning from phagocytosis modulation and direct engagement with across various pathological scenarios. Comprehensive understanding OPCs alongside other roles will pave way for targeted therapies in neurological disorders.
Язык: Английский
Процитировано
3