Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia
Abstract
Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.
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ATRA-containing nanoparticles enhanced endothelial cell proliferation and tubule network formation and protected against ischemia-induced death in endothelial cell lines and endothelial progenitor cells isolated from ischemic stroke patients.
“The formulation enhanced endothelial cell proliferation and tubule network formation and protected against ischemia-induced death in endothelial cell lines and endothelial progenitor cells isolated from ischemic stroke patients24.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [24]
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- Authors
- Ferreira, R., Fonseca, M. C., Santos, T., Sargento-Freitas, J., Tjeng, R., Paiva, F., Castelo-Branco, M., Ferreira, L. S., & Bernardino, L.
- Affiliations
- University of Beira Interior (PT)
- Hospital Center of Cova da Beira (PT)
- Biocant – Associação de Transferência de Tecnologia (PT)
- Corresponding author
- Ferreira, R.
- Bernardino, L.
- Venue
- Nanoscale
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2016
- Volume
- 8
- Issue
- 15
- Pages
- 8126-8137
- ISSN
- 2040-3364 (ISSN-L)
- 2040-3372
- OpenAlex
- W2316582610
- Cited by
- 44
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 8 · 2016: 2
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nanoscale (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia (EXPL/BIM-MED/0822/2013, SFRH/BD/79526/2011, SFRH/BPD/94228/2013, UID/Multi/00709/2013)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- retinoic acid, polymeric nanoparticles, ischemic stroke, neural stem cells, endothelial cells, angiogenesis, endothelial progenitor cells, neurogenesis, neuronal differentiation, neuroprotection, vascular regulation, nanoparticle drug delivery
- MeSH terms
- Animals, Cell Differentiation, Cell Survival, Drug Carriers, Humans, Ischemia, Polymers, Tretinoin, Cell Death, Neovascularization, Physiologic, Stroke, Cell Proliferation, Mice, Nanoparticles, Neurogenesis, Neural Stem Cells
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