Stem cells in central nervous system diseases: Promising therapeutic strategies DOI Creative Commons

Caidi Ying,

Jiahao Zhang, Haocheng Zhang

et al.

Experimental Neurology, Journal Year: 2023, Volume and Issue: 369, P. 114543 - 114543

Published: Sept. 23, 2023

Central nervous system (CNS) diseases are a leading cause of death and disability. Due to CNS neurons have no self-renewal regenerative ability as they mature, their loss after injury or disease is irreversible often leads functional impairments. Unfortunately, therapeutic options for still limited, effective treatments these notorious warranted be explored. At present, stem cell therapy has emerged potential strategy improving the prognosis diseases. Accumulating preclinical clinical evidences demonstrated that multiple molecular mechanisms, such replacement, immunoregulation neurotrophic effect, underlie use However, several issues yet addressed support its application. Thus, this review article aims summarize role underlying mechanisms in treating And it worthy further evaluation applications treatment disease.

Language: Английский

Dental-Derived Mesenchymal Stem Cells: State of the Art DOI Creative Commons
Bo Li, Takehito Ouchi, Yubin Cao

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: June 22, 2021

Mesenchymal stem cells (MSCs) could be identified in mammalian teeth. Currently, dental-derived MSCs (DMSCs) has become a collective term for all the isolated from dental pulp, periodontal ligament, follicle, apical papilla, and even gingiva. These DMSCs possess similar multipotent potential as bone marrow-derived MSCs, including differentiation into that have characteristics of odontoblasts, cementoblasts, osteoblasts, chondrocytes, myocytes, epithelial cells, neural hepatocytes, adipocytes. Besides, also powerful immunomodulatory functions, which enable them to orchestrate surrounding immune microenvironment. properties promising approach injury repair, tissue regeneration, treatment various diseases. This review outlines most recent advances DMSCs’ functions applications enlightens how these are paving path DMSC-based therapies.

Language: Английский

Citations

76

Mesenchymal Stem Cell-Based Therapy for Stroke: Current Understanding and Challenges DOI Creative Commons
Weifeng Li, Linli Shi, Bei Hu

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Feb. 9, 2021

Stroke, the most prevalent cerebrovascular disease, causes serious loss of neurological function and is leading cause morbidity mortality worldwide. Despite advances in pharmacological surgical therapy, treatment for functional rehabilitation following stroke limited with a consequent impact on quality life. Over past decades, mesenchymal stem cell (MSCs)-based therapy has emerged as novel strategy various diseases including due to their unique properties that include easy isolation, multipotent differentiation potential strong paracrine capacity. Although MSCs have shown promising results stroke, there remain many challenges overcome prior therapeutic application. In this review, we focus issues: scientific data from preclinical studies clinical trials stroke; mechanisms underlying MSC-based related timing delivery MSC senescence.

Language: Английский

Citations

72

Advances in clinical translation of stem cell-based therapy in neurological diseases DOI
Yu Wang,

Yirong Cao,

Wanqing Xie

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Stem cell-based therapies have raised considerable interest to develop regenerative treatment for neurological disorders with high disability. In this review, we focus on recent preclinical and clinical evidence of stem cell therapy in the degenerative diseases discuss different types, delivery routes biodistribution therapy. addition, advances mechanistic insights therapy, including functional replacement by exogenous cells, immunomodulation paracrine effects are also demonstrated. Finally, highlight adjunction approaches that has been implemented augment their reparative function, survival migration target specific tissue, preconditioning, genetical engineering, co-transplantation combined

Language: Английский

Citations

1

Potential Mechanisms and Perspectives in Ischemic Stroke Treatment Using Stem Cell Therapies DOI Creative Commons

Guoyang Zhou,

Yongjie Wang,

Shiqi Gao

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: April 1, 2021

Ischemic stroke (IS) remains one of the major causes death and disability due to limited ability central nervous system cells regenerate differentiate. Although several advances have been made in therapies last decades, there are only a few approaches available improve IS outcome. In acute phase IS, mechanical thrombectomy administration tissue plasminogen activator widely used, while aspirin or clopidogrel represents main therapy used subacute chronic phase. However, most cases, patients fail achieve satisfactory functional recovery under treatments mentioned above. Recently, cell therapy, especially stem has considered as novel potential therapeutic strategy outcome through mechanisms, including differentiation, replacement, immunomodulation, neural circuit reconstruction, protective factor release. Different types, such mesenchymal cells, marrow mononuclear also for therapy. recent years, many clinical preclinical studies on carried out, numerous results shown that bright prospects treatment stroke. some issues not yet fully understood, its optimal parameters type choice, doses, injection routes; therefore, closer relationship between basic research is needed. this review, role mechanisms was summarized, well function different types trials using cure stroke, reveal future insights stroke-related guide further studies.

Language: Английский

Citations

39

Proteomic Characterization of Human Neural Stem Cells and Their Secretome During in vitro Differentiation DOI Creative Commons
Jakub Červenka,

Jiřina Tylečková,

Helena Kupcová Skalníková

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: Jan. 28, 2021

Cell therapies represent a promising approach to slow down the progression of currently untreatable neurodegenerative diseases (e.g., Alzheimer's and Parkinson's disease or amyotrophic lateral sclerosis), as well support reconstruction functional neural circuits after spinal cord injuries. In such therapies, grafted cells could either functionally integrate into damaged tissue, partially replacing dead cells, modulate inflammatory reaction, reduce tissue damage, neuronal survival by secretion cytokines, growth, trophic factors. Comprehensive characterization their proliferative potential, differentiation status, population purity before transplantation is crucial preventing safety risks, e.g., tumorous growth due proliferation undifferentiated stem cells. We characterized changes in proteome secretome human (NSCs) during spontaneous (EGF/FGF2 withdrawal) with BDNF/GDNF supplementation. used LC-MS/MS SWATH-MS mode for global cellular profiling quantified almost three thousand proteins. Our analysis identified substantial protein differences early stages NSC more than third all proteins regulated (including known multipotency markers) revealed that affected later differentiation. Among pathways activated both were HIF-1 signaling pathway, Wnt VEGF pathway. follow-up using Luminex multiplex immunoassay significant IL-6 results further demonstrated an increased expression neuropilin-1 catenin β-1, participate regulation signaling, showed VEGF-A isoform 121 (VEGF121), particular, induces supports differentiating

Language: Английский

Citations

35

Current status of ischemic stroke treatment: From thrombolysis to potential regenerative medicine DOI Creative Commons

Mason Daniel Hurd,

Isha Goel, Yasuyuki Sakai

et al.

Regenerative Therapy, Journal Year: 2021, Volume and Issue: 18, P. 408 - 417

Published: Oct. 13, 2021

Ischemic stroke is a major cause of death and disability worldwide expected to increase in the future with aging population. Currently, there are no clinically available treatments for damage sustained during an ischemic stroke, but much research being conducted this area. In review, we will introduce current along their limitations, as well on potential short long-term treatments. There advantages disadvantages these treatments, our understanding methods effectiveness clinical trials improving. We confident that some introduced review become commonly used settings future.

Language: Английский

Citations

35

Receptors, Channel Proteins, and Enzymes Involved in Microglia-mediated Neuroinflammation and Treatments by Targeting Microglia in Ischemic Stroke DOI
Kun Hou, Guichen Li, Jinlu Yu

et al.

Neuroscience, Journal Year: 2021, Volume and Issue: 460, P. 167 - 180

Published: Feb. 19, 2021

Language: Английский

Citations

33

Aberrant branched‐chain amino acid accumulation along the microbiota–gut–brain axis: Crucial targets affecting the occurrence and treatment of ischaemic stroke DOI Open Access
Jiajia Shen, Huimin Guo,

Shijia Liu

et al.

British Journal of Pharmacology, Journal Year: 2022, Volume and Issue: 180(3), P. 347 - 368

Published: Oct. 1, 2022

Although increasing evidence illustrated that the bidirectional communication between brain and gut is closely related to occurrence of various complex diseases. Limited effort has been made explore influence intestinal flora on risk ischaemic stroke. The present study aims identify microbiota specialized metabolites treatment stroke.The role in stroke was evaluated ischaemia/reperfusion (I/R), pseudo-germ-free faecal transplantation animals. target were identified by comparing their distribution metabolomic profiles patients animals with compared healthy controls. effects mechanisms involved targeted explored rats, hypoxia/reoxygenation PC12 cells LPS-induced inflammatory BV2 cells.Both I/R rats had significant accumulation branched-chain amino acids, which associated microflora dysbiosis development Lactobacillus helveticus (L.hel) brevis (L.bre) are as most affected modelling treatment. L.hel L.bre colonization exhibited neuroprotective activity could greatly alleviate acids. In addition, acid (BCAA) shown exacerbate microglia-induced neuroinflammation activating AKT/STAT3/NF-κB signalling.Our findings demonstrated crucial

Language: Английский

Citations

28

Shh and Olig2 sequentially regulate oligodendrocyte differentiation from hiPSCs for the treatment of ischemic stroke DOI Creative Commons
Jian Xu,

Jingxin Zhao,

Rui Wang

et al.

Theranostics, Journal Year: 2022, Volume and Issue: 12(7), P. 3131 - 3149

Published: Jan. 1, 2022

Rationale: Demyelination is a major component of white matter injury, characterized by oligodendrocyte (OL) death and myelin sheath loss, which result in memory loss cognitive impairment the context ischemic stroke.Accumulating evidence has shown that OLs can be generated direct activation defined transcription factors (TFs) human induced pluripotent stem cells (hiPSCs); however, rapid acquisition single TF-induced OL progenitor (OPCs) as cell therapy for stroke remains to thoroughly explored.Methods: A stable, chemically protocol was used generate substantial number transplantable functional through partial inhibition sonic hedgehog (Shh) activity GANT61 during neural induction from hiPSCs sequential TF Olig2 overexpression.Transcriptome metabolome analyses further revealed novel molecular event regulates differentiation hiPSC-derived (NPCs).Olig2-induced NG2 + OPCs (Olig2-OPCs) were then evaluated their therapeutic potential cell-based stroke.Results: treatment resulted motor neuron (MN)-OL fate switch induction, overexpression accelerated oligodendroglial lineage specification.Olig2-OPCs expressed typical marker genes, including NKX2.2, CSPG4, ST8SIA1, displayed superior ability differentiate into mature vitro.Mechanistically, Olig2-OPCs showed increased gene expression peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway, activated CEPT1-mediated phospholipogenesis.Functionally, inhibiting PPARγ knocking down CEPT1 compromised terminal Olig2-OPCs.Most importantly, when transplanted rat model transient middle cerebral artery occlusion (tMCAO), efficiently promoted neurological recovery reducing neuronal death, promoting remyelination, rescuing spatial decline.Conclusions: We developed OPCs/OLs with Shh sequentially Olig2.Olig2-OPC transplantation may an ideal alternative approach rehabilitation therapy.

Language: Английский

Citations

25

Hydrogel-Based Therapies for Ischemic and Hemorrhagic Stroke: A Comprehensive Review DOI Creative Commons
Alexandra Daniela Rotaru-Zavaleanu, Venera Cristina Dinescu,

Mădălina Aldea

et al.

Gels, Journal Year: 2024, Volume and Issue: 10(7), P. 476 - 476

Published: July 18, 2024

Stroke remains the second leading cause of death and a major disability worldwide, significantly impacting individuals, families, healthcare systems. This neurological emergency can be triggered by ischemic events, including small vessel arteriolosclerosis, cardioembolism, large artery atherothromboembolism, as well hemorrhagic incidents resulting from macrovascular lesions, venous sinus thrombosis, or vascular malformations, to significant neuronal damage. The resultant motor impairment, cognitive dysfunction, emotional disturbances underscore urgent need for effective therapeutic interventions. Recent advancements in biomaterials, particularly hydrogels, offer promising new avenues stroke management. Hydrogels, composed three-dimensional networks hydrophilic polymers, are notable their ability absorb retain substantial amounts water. Commonly used polymers hydrogel formulations include natural like alginate, chitosan, collagen, synthetic such polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyacrylamide. Their customizable characteristics—such porosity, swelling behavior, mechanical strength, degradation rates—make hydrogels ideal biomedical applications, drug delivery, cell tissue engineering, controlled release agents. review comprehensively explores hydrogel-based approaches both therapy, elucidating mechanisms which provide neuroprotection. It covers application delivery systems, role reducing inflammation secondary injury, potential support neurogenesis angiogenesis. also discusses current technology challenges translating these innovations research into clinical practice. Additionally, it emphasizes limited number trials utilizing therapies addresses associated limitations constraints, underscoring further this field.

Language: Английский

Citations

5