ArticleFrontiers in aging neuroscience2021
Intranasal Transplantation of Human Neural Stem Cells Ameliorates Alzheimer's Disease-Like Pathology in a Mouse Model.
Article in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Intranasal administration of stem cell derivatives for the treatment of AD animal models: a systematic review and meta-analysis.Stem cell research & therapy · 2025Pooled it
- Neural stem/progenitor cell therapy for Alzheimer disease in preclinical rodent models: a systematic review and meta-analysis.Stem cell research & therapy · 2023Pooled it
- Neural Stem/Progenitor Cells Regulate Neuroinflammation: Mechanisms and Therapeutic Applications in Neurological Diseases.International journal of molecular sciences · 2026Review
- Review
- Pathophysiological roles of neural stem cells in neuropsychiatric diseases: from plasticity to pharmacological targeting.Acta pharmacologica Sinica · 2026Review
- From Traumatic Brain Injury to Alzheimer's Disease: Multilevel Biomechanical, Neurovascular, and Molecular Mechanisms with Emerging Therapeutic Directions.International journal of molecular sciences · 2026Review
- Long-Term Effects of Xenotransplantation of Human Enteric Glia in an Immunocompetent Rat Model of Acute Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modulation of BDNF/TrkB Signalling Pathway in Alzheimer's Disease: Mechanistic Insights and the Role of Stem Cell Therapy.Biomedicines · 2025Review
- Therapeutic Applications of Dental Mesenchymal Stem Cells in Alzheimer's Disease-A Scoping Review.Dentistry journal · 2025Review
- Intranasal Drug Delivery Technology in the Treatment of Central Nervous System Diseases: Challenges, Advances, and Future Research Directions.Pharmaceutics · 2025Review
- Nose-to-brain drug delivery: from bench to bedside.Translational neurodegeneration · 2025Review
- Effect of Small Extracellular Vesicles Produced by Mesenchymal Stem Cells on 5xFAD Mice Hippocampal Cultures.International journal of molecular sciences · 2025Article
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- Non-pharmacological treatment of Alzheimer's disease: an update.Frontiers in aging neuroscience · 2025Review
- Electroacupuncture Preconditioning Ameliorates the Ischemic Microenvironment to Improve Long-Term Potentiation in Chronic Cerebral Hypoperfusion Rats With MGE Neural Progenitor Transplantation.Neural plasticity · 2025Article
- Extracellular vesicles from human-induced pluripotent stem cell-derived neural stem cells alleviate proinflammatory cascades within disease-associated microglia in Alzheimer's disease.Journal of extracellular vesicles · 2024Article
- Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer's disease.Neural regeneration research · 2024Review
- GR/Ahi1 regulates WDR68-DYRK1A binding and mediates cognitive impairment in prenatally stressed offspring.Cellular and molecular life sciences : CMLS · 2024Article
- Therapeutic role of neural stem cells in neurological diseases.Frontiers in bioengineering and biotechnology · 2024Review
- Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.Open life sciences · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairments, which has no effective therapy. Stem cell transplantation shows great potential in the therapy of various disease. However, the application of stem cell therapy in neurological disorders, especially the ones with a long-term disease course such as AD, is limited by the delivery approach due to the presence of the brain blood barrier. So far, the most commonly used delivery approach in the therapy of neurological disorders with stem cells in preclinical and clinical studies are intracranial injection and intrathecal injection, both of which are invasive. In the present study, we use repetitive intranasal delivery of human neural stem cells (hNSCs) to the brains of APP/PS1 transgenic mice to investigate the effect of hNSCs on the pathology of AD. The results indicate that the intranasally transplanted hNSCs survive and exhibit extensive migration and higher neuronal differentiation, with a relatively limited glial differentiation. A proportion of intranasally transplanted hNSCs differentiate to cholinergic neurons, which rescue cholinergic dysfunction in APP/PS1 mice. In addition, intranasal transplantation of hNSCs attenuates β-amyloid accumulation by upregulating the expression of β-amyloid degrading enzymes, insulin-degrading enzymes, and neprilysin. Moreover, intranasal transplantation of hNSCs ameliorates other AD-like pathology including neuroinflammation, cholinergic dysfunction, and pericytic and synaptic loss, while enhancing adult hippocampal neurogenesis, eventually rescuing the cognitive deficits of APP/PS1 transgenic mice. Thus, our findings highlight that intranasal transplantation of hNSCs benefits cognition through multiple mechanisms, and exhibit the great potential of intranasal administration of stem cells as a non-invasive therapeutic strategy for AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.