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Stem Cell-Derived Extracellular Vesicles Ameliorate the Neuron Mitochondrial Damage Induced by ROS-, LPS-Exposure: In Vitro Model of Neuron, Microglia, and Astrocyte Triple Co-Culture
Marta Malenchini, Francesca Beretti, Martina Gatti, Emma Bertucci, Elena Del Toro, Tullia Maraldi. International Journal of Molecular Sciences, 2026-05-27
Topic: Brain proteins, microglia and lab models
Oxidative stress causes brain damage contributing to neurodegenerative and vascular diseases. In Alzheimer’s disease (AD), elevated oxidative stress and mitochondrial damage are closely linked to misfolded protein accumulation. ROS also plays a major role in ischemic brain injury, particularly during reperfusion, impairing the blood–brain barrier and highlighting the association between vascular pathology and AD. To investigate perturbations in brain cells occurring in mixed dementia (AD combined with vascular dementia components), we used a triple culture system comprising neurons, astrocytes, and microglia and induced neuronal injury by combining LPS and H2O2 exposures. Cell viability assays revealed that neuronal death occurred mainly through apoptosis and DNA damage. In neurons and astrocytes exposed to LPS+H2O2, the expression of NADPH oxidase isoform 2, a major source of ROS, increased, along with FOXO3 and SOD2, a key mitochondrial ROS scavenger. Indeed, these changes were accompanied by altered mitochondrial morphology and integrity, as well as reduced neurite extension and thickness. The treatment with extracellular vesicles (EVs) derived from amniotic fluid stem cells was tested due to their rich content of antioxidant molecules. Interestingly, EVs reversed the negative effects of LPS+H2O2, suggesting the protective role against neuronal injury in vitro may be mediated by the EV-cargo.
Key findings
- Cell viability assays revealed that neuronal death occurred mainly through apoptosis and DNA damage.
Why it matters
In a laboratory triple culture of neurons, astrocytes, and microglia, extracellular vesicles from amniotic fluid stem cells reversed damage caused by LPS and hydrogen peroxide. This is in-vitro research, so it does not yet show a treatment for Alzheimer's disease in people.
Study details
- Evidence strengthLow
How this study scored 37/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International Journal of Molecular Sciences) |
| Journal's citation record | 3 / 4 | International Journal of Molecular Sciences: journal h-index 426 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “in vitro”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 2 / 6 | Cited 1.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Tullia Maraldi: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Bologna: institution h-index 989 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42278362) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3390/ijms27114834
- PubMed: 42278362
- Original source →
- Free full text: International Journal of Molecular Sciences →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Malenchini, M., Beretti, F., Gatti, M., Bertucci, E., Del Toro, E., & Maraldi, T. (2026). Stem Cell-Derived Extracellular Vesicles Ameliorate the Neuron Mitochondrial Damage Induced by ROS-, LPS-Exposure: In Vitro Model of Neuron, Microglia, and Astrocyte Triple Co-Culture. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms27114834
Vancouver
Malenchini M, Beretti F, Gatti M, Bertucci E, Del Toro E, Maraldi T. Stem Cell-Derived Extracellular Vesicles Ameliorate the Neuron Mitochondrial Damage Induced by ROS-, LPS-Exposure: In Vitro Model of Neuron, Microglia, and Astrocyte Triple Co-Culture. International Journal of Molecular Sciences. 2026. doi:10.3390/ijms27114834. PMID: 42278362.
BibTeX
@article{malenchini2026-42278362,
author = {Malenchini, Marta and Beretti, Francesca and Gatti, Martina and Bertucci, Emma and Del Toro, Elena and Maraldi, Tullia},
title = {{Stem Cell-Derived Extracellular Vesicles Ameliorate the Neuron Mitochondrial Damage Induced by ROS-, LPS-Exposure: In Vitro Model of Neuron, Microglia, and Astrocyte Triple Co-Culture}},
journal = {International Journal of Molecular Sciences},
year = {2026},
doi = {10.3390/ijms27114834},
pmid = {42278362},
url = {https://doi.org/10.3390/ijms27114834}
}
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