ArticleCell death and differentiation2021
Intranasal delivery of mesenchymal stem cell secretome repairs the brain of Alzheimer's mice.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 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
- Intracerebroventricular human mesenchymal stem cells induce MMP9-driven transient inflammation in Alzheimer's disease.Stem cell research & therapy · 2026Trial
- Exosomes in Alzheimer's Disease: From Pathological Mechanisms to Biomarker Potential and Therapeutic Applications.Molecular neurobiology · 2026Review
- Collecting Eggs, Not Killing Chickens: Why Stem Cell Secretome and Exosomes Are Redefining Regenerative Medicine for Healthspan Extension.Biomedicines · 2026Review
- Shear-Induced CROSS (Cellular RedOx Spreading Shield) Assembly Sustains Neurotrophic Extracellular Vesicle Production for Functional Neural Networks.Advanced functional materials · 2026Article
- Potential of intranasal delivery of human mesenchymal stem cells and extracellular vesicles for stroke therapy.Acta biomaterialia · 2026Review
- Therapeutic Efficacy of Mesenchymal Stem Cells (MSCs) on Alzheimer's Disease: Review of Clinical Results.Tissue engineering and regenerative medicine · 2026Review
- Micro/Nanoparticles in the Nose-Brain Axis: Implications for Pathogenesis and Therapeutic Interventions.International journal of nanomedicine · 2026Review
- A Review of The Place of Adipose-Derived Stem Cells among Stem Cell Applications in Neurodegenerative Diseases.Current topics in medicinal chemistry · 2026Review
- Engineered Source-Specific Extracellular Vesicles for Neurodegenerative Diseases: From Biological Barriers to Targeted Delivery Strategies.International journal of nanomedicine · 2026Review
- Mesenchymal stem cells and the central nervous system: historical perspectives and future directions.Frontiers in molecular neuroscience · 2026Review
- Cell-Free Therapies for Chronic Pain: The Rise of the Mesenchymal Stem Cell Secretome.Brain sciences · 2025Review
- Effectiveness of Insulin-Induced umbilical cord stem cells on Seladin-1/APP/GFAP expression in rat hippocampal CA1/CA3 regions following chronic hypoxia.Journal of molecular histology · 2025Article
- Nose-to-brain drug delivery: from bench to bedside.Translational neurodegeneration · 2025Review
- Cell-based regenerative and rejuvenation strategies for treating neurodegenerative diseases.Stem cell research & therapy · 2025Review
- Article
- CD4-Derived Double-Negative T Cells Ameliorate Alzheimer's Disease-Like Phenotypes in the 5×FAD Mouse Model.CNS neuroscience & therapeutics · 2025Article
- Boosting the Therapeutic Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells via Advanced Preconditioning for Neurodegenerative Disorders.Stem cells international · 2025Review
- Stem cell extracellular vesicles: a new dawn for anti-inflammatory treatment of neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Clinical-grade human dental pulp stem cells improve adult hippocampal neural regeneration and cognitive deficits in Alzheimer's disease.Theranostics · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multiplicity of systems affected in Alzheimer's disease (AD) brains calls for multi-target therapies. Although mesenchymal stem cells (MSC) are promising candidates, their clinical application is limited because of risks related to their direct implantation in the host. This could be overcome by exploiting their paracrine action. We herein demonstrate that in vivo systemic administration of secretome collected from MSC exposed in vitro to AD mouse brain homogenates (MSC-CS), fully replicates the cell-mediated neuroreparative effects in APP/PS1 AD mice. We found a complete but transient memory recovery by 7 days, which vanished by 14 days, after a single MSC-CS intravenous administration in 12-month or 22-24-month-old mice. Treatment significantly reduced plaque load, microglia activation, and expression of cytokines in astrocytes in younger, but not aged, mice at 7 days. To optimize efficacy, we established a sustained treatment protocol in aged mice through intranasal route. Once-weekly intranasal administration of MSC-CS induced persistent memory recovery, with dramatic reduction of plaques surrounded by a lower density of β-amyloid oligomers. Gliosis and the phagocytic marker CD68 were decreased. We found a higher neuronal density in cortex and hippocampus, associated with a reduction in hippocampal shrinkage and a longer lifespan indicating healthier conditions of MSC-CS-treated compared to vehicle-treated APP/PS1 mice. Our data prove that MSC-CS displays a great multi-level therapeutic potential, and lay the foundation for identifying the therapeutic secretome bioreactors leading to the development of an efficacious multi-reparative cocktail drug, towards abrogating the need for MSC implantation and risks related to their direct use.
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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.