Advances in genetically modified neural stem cell therapy for central nervous system injury and neurological diseases

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 18, 2024

Neural stem cells (NSCs) have increasingly been recognized as the most promising candidates for cell-based therapies central nervous system (CNS) injuries, primarily due to their pluripotent differentiation capabilities, well remarkable secretory and homing properties. In recent years, extensive research efforts initiated explore therapeutic potential of NSC transplantation CNS yielding significant advancements. Nevertheless, owing formation adverse microenvironment at post-injury leading suboptimal survival, differentiation, integration within host neural network transplanted NSCs, NSC-based often fall short achieving optimal outcomes. To address this challenge, genetic modification has developed an attractive strategy improve outcomes therapies. This is mainly attributed its not only enhance capacity NSCs but also boost a range biological activities, such secretion bioactive factors, anti-inflammatory effects, anti-apoptotic properties, immunomodulation, antioxidative functions, angiogenesis. Furthermore, empowers play more robust neuroprotective role in context nerve injury. review, we will provide overview advances roles mechanisms genetically modified with various genes treatment injuries disorders. Also, update on current technical parameters suitable functional recovery clinical studies are summarized.

Language: Английский

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Unraveling the role of oligodendrocytes and myelin in pain

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 169(1)

Published: Aug. 20, 2024

Oligodendrocytes, the myelin-producing cells in central nervous system (CNS), are crucial for rapid action potential conduction and neuronal communication. While extensively studied their roles support axonal insulation, involvement pain modulation is an emerging research area. This review explores interplay between oligodendrocytes, myelination, pain, focusing on neuropathic following peripheral nerve injury, spinal cord injury (SCI), chemotherapy, HIV infection. Studies indicate that a decrease oligodendrocytes increased cytokine production by oligodendroglia response to can induce or exacerbate pain. An increase endogenous oligodendrocyte precursor (OPCs) may be compensatory repair damaged oligodendrocytes. Exogenous OPC transplantation shows promise alleviating SCI-induced enhancing remyelination. Additionally, apoptosis brain regions such as medial prefrontal cortex linked opioid-induced hyperalgesia, highlighting role mechanisms. Chemotherapeutic agents disrupt differentiation, leading persistent while HIV-associated neuropathy involves up-regulation of lineage cell markers. These findings underscore multifaceted pathways, suggesting targeting myelination processes could offer new therapeutic strategies chronic management. Further should elucidate underlying molecular mechanisms develop effective treatments.

Language: Английский

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Harnessing therapeutic potential of induced pluripotent stem cell–derived endothelial cells for remyelination in the central nervous system

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(6), P. 1715 - 1716

Published: June 26, 2024

Myelin is the protective sheath surrounding nerve fibers, and its damage (demyelination) occurs in many central nervous system (CNS) diseases, including multiple sclerosis (MS), traumatic injury, neurodegenerative diseases such as Alzheimer's disease, mental disorders schizophrenia (Barateiro et al., 2016). Repair of damaged myelin sheaths (remyelination) often fails MS, leading to neuronal loss irreversible functional deficits. Remyelination involves activation recruitment adult oligodendrocyte progenitor cells (OPCs), residential stem CNS, which eventually differentiate into new mature oligodendrocytes form on demyelinated axons. Promoting remyelination emerges a potentially effective clinical intervention for broad range demyelinating progressive MS (Franklin Ffrench-Constant, 2017). Currently, there no treatment directly promoting clinic. In recent years, advances cell research have paved way innovative approaches treating neurological disorders. One promising avenue use human induced pluripotent (iPSC)-derived promote CNS. iPSCs potential almost all types, making them source conditions requiring tissue graft. Patient-specific iPSC-derived not only been widely used model various research, but they also shown application wide variety devastating diseases. Induced cell-derived remyelination: Several types explored therapy enhancing animal models, embryonic cells-derived neural OPCs, precursor cells, OPCs bone marrow mesenchymal stromal (Christodoulou 2024). Exogenously administered exert beneficial effect following demyelination through replacement or/and modulation immunomodulation, extracellular matrix remodeling, nutritional support, neuroprotection, stimulating endogenous remyelination. These effects are predominantly attributed secretome transplanted consists soluble factors vesicles (Daneshmandi 2020). For current mainly focuses myelin-producing cells. iPSCs-derived generated by varying induction protocols capable myelinating host axons mouse models congenital hypomyelination, CNS demyelination, spinal cord injury (McCaughey-Chapman Connor, 2023). The challenge remains obtaining population from with high efficiency. lineage transplantation mostly O4+ population, immature pre-myelinating (preOLs). PreOLs post-mitotic able expand vitro, their limited compared progenitors. Nevertheless, preOLs has therapeutic (Figure 1). Whether OPCs/preOLs can remyelinate after brain unknown.Figure 1: hold system.iPSC-derived remyelinating together Created BioRender.com. hiPSC: Human cell; OL: oligodendrocyte; OPC: cell.In addition replacing astrocytic-fated progenitors increase oligodendrogenesis via release growth mice white matter stroke (Llorente 2021). Recently it reported that long-term neuroepithelial produce bona fide oligodendrocytes, these myelinate culture, rat stroke-injured cortex organotypic cultures (Martinez-Curiel findings provide encouraging evidence future lines recovery injuries. associated dynamic microenvironment. success generation provided practical specific types. It expected more efforts exploring other therapy. endothelial Endothelial (ECs) cerebral blood vessels secrete trophic FGF brain-derived neurotrophic factor (BDNF) sustain OPC proliferation, survival, differentiation (Arai Lo, 2009). ECs (iPSC-ECs) be improve restoration ischemic heart, limb, brain, wound healing either direct or interaction (Jang 2019). Recently, Ishizaki's lab our iPSC-ECs different models. Transplantation improves damage; this increased number suppressed inflammatory response, regulatory T (Xu We tested exogenous toxin-induced showed promoted repair BDNF, enhanced linage progression activating mTORC1 signaling pathway. addition, M2 polarization microglia, synergistically regeneration (Ma exact cellular molecular mechanisms underlying properties yet fully elucidated. However, results further substantiate suggestion injuries Dynamic cell-endothelial progression: multifaceted impact environment, contributed produced locally, circulation. Within local microenvironment, areas orchestrate process. Microglia astrocytes cytokines factors, secret molecules, clear debris, create conducive environment OPCs. during correlates switch proinflammatory M1 microglia/A1 astrocyte pro-regenerative M2/A2 phenotypes. transition neuroinflammation profile facilitates stage-specific microenvironment required maturation successful biologically active secreted ECs, come vehicles, contain cocktail proved proliferation differentiation. Among them, BDNF well known support survival whereas transforming β individually enhance maturation. Since two inversely related processes usually coincides arrest, enhancement exposure likely sequentially mediated pathways. Moreover, some may play roles context-dependent manner, thereby modulating then interacting additional factors. Hence, EC's holds repair. past decade, secretome-based therapies emerged approach overcome limitations cell-based organ signature EC importance still established. Furthermore, reasonable speculate affected oligodendrocytes. interact both released physical contact regulate functions mutually (Chavali conceivable status changing interactions present pre-maturation characteristics 2019), therefore resemble nascent while less specialized ECs. This enable Thus, between shapes environment. essential rebuilding vasculature damage, towards situations, impairment due pathological ageing, healthy will help restore network, therefore, 2). might benefits blood-brain barrier stability, inflammation, immune infiltration.Figure 2: CNS.iPSC-EC secretome, vesicles, affects network involved damage. CNS: Central system; EC: hiPSC-EC: hiPSC-derived EC; cell. ●: Extracellular vesicles; •••: molecules/soluble factors.Therapeutic diseases: Demyelinating group cause most common disease caused autoimmune attack. Others include optic neuritis, neuromyelitis optica spectrum disorder, glycoprotein antibody-associated disease. revealed example, suggested breakdown plays role development found dysfunction component Schizophrenia. ischemia/stroke contributes recovery. represent complex context myelin-related Therefore, should assessed according individual characteristics. Although iPSC-OPCs derived faster higher efficiency, challenges existing. As replace combination obtain advantages purposes, integration existing (Li Overall, studies suggest benefit protection regeneration, providing Developing interventions using presents direction translation. iPSC technology enabled scalable consistent patient-specific offering renewable precision platform. Challenges considerations: Despite great promise, several iPSC-EC settings. need safety measures, propensity teratomas vivo, especially Safe, efficient, functional, thoroughly before reaching trial. Immunogenicity considered when differentiated ready-to-go allogeneic transplantations Another delivery. Many involving exhibit regions disseminated form, grafting sites extremely challenging. Other delivery routes intraventricular intranasal tested. timing, frequency, duration, dosage optimized. harnessing regenerative unlock transformative treatments target causes disability affecting Future focus refining protocols, combinatorial strategies, conducting preclinical trials validate efficacy approach. work was supported grant Aston University, Birmingham, UK (to DM). C-Editors: Zhao M, Liu WJ, Qiu Y; T-Editor: Jia Y

Language: Английский

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Neurophilic peptide-reinforced dual-fiber-network bioactive hydrogels for spinal cord injury repair

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 498, P. 155301 - 155301

Published: Aug. 30, 2024

Language: Английский

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Advances in human pluripotent stem cell reporter systems

iScience, Journal Year: 2024, Volume and Issue: 27(9), P. 110856 - 110856

Published: Aug. 30, 2024

Language: Английский

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Modern cell culture technologies: Revolutionizing neuroregeneration in neuropsychiatry

Archives of Biological Psychiatry, Journal Year: 2024, Volume and Issue: 2, P. 14 - 24

Published: July 6, 2024

This review highlights the latest developments in current cell culture methods, including three-dimensional culture, organoids, coculture systems, microfluidics, and nanofiber scaffolds to support neuroregeneration major neuropsychiatric illnesses. Due enhanced vitro modeling of human brain structure function, these state-of-the-art methods allow for investigations disease processes drug screening, pathophysiological research on has increased. We examine recent relationship between technologies conditions such as stroke, Alzheimer’s, traumatic injury, spinal cord injury. The advancements present encouraging prospects augmenting could facilitate stem cell-based therapies ailments that were previously untreatable.

Language: Английский

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