Multifunctionalized hydrogels foster hNSC maturation in 3D cultures and neural regeneration in spinal cord injuries
Open accessAbstract
Significance: Cells reside in 3D microenvironments in living tissues; consequently, 3D cultures gained great interest because they better mimic the natural conditions of cells. Self-assembling peptides (SAPs) are synthetic bioabsorbable biomaterials that can provide customized 3D microenvironments regulating cell functionalities and tissue repair. Here we introduce a SAP-hydrogel designed to support human neural stem cell (hNSC) differentiation in 3D serum-free conditions, generating mature and active human neurons in vitro. We also demonstrate its functional neurorigenerative potential in rat spinal cord injuries, peaking when seeded with hNSCs progeny predifferentiated in vitro for 6 weeks. Despite these promising results, this approach should be confirmed in the future with medium-size animal models and with additional and refined behavioral tests before entering a clinical trial.
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HYDROSAP peptide 3D hydrogels with elastic moduli of ~800 Pa (similar to the stiffness of human brain tissue) were used to culture human fetal neural stem cells, which were able to differentiate into various lineages including astrocytes, oligodendrocytes, and neurons.
“The authors used HYDROSAP peptide 3D hydrogels with elastic moduli of ~800 Pa (similar to the stiffness of human brain tissue) to culture human fetal neural stem cells198, which were able to differentiate into various lineages including astrocytes, oligodendrocytes, and neurons.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [198]
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References 65 · Cited by 99
- Authors
- Marchini, A., Raspa, A., Pugliese, R., El Malek, M. A., Pastori, V., Lecchi, M., Vescovi, A. L., & Gelain, F.
- Affiliations
- Casa Sollievo della Sofferenza (IT)
- Center for Nanomedicine and Tissue Engineering, ASST Ospedale Metropolitano Niguarda, 20162 Milan, Italy;
- University of Milano-Bicocca (IT)
- Corresponding author
- Gelain, Fabrizio
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-03-28
- Volume
- 116
- Issue
- 15
- Pages
- 7483-7492
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6462084
- OpenAlex
- W2923712477
- Cited by
- 99
- References
- 65
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 10 · 2023: 18 · 2022: 13 · 2021: 23 · 2020: 23 · 2019: 3
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion, other-oa)
- Funders
- Ministero della Salute (Ricerca Corrente 2018-2020)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- hydrogels, human neural stem cells, spinal cord injury, nerve regeneration, 3D cell culture, neuronal differentiation, GABAergic neurons, glutamatergic neurons, cholinergic neurons, artificial neural networks, cell transplantation, astrocyte activation, immune response, engraftment, behavioral recovery, serum-free medium
- MeSH terms
- Animals, Cell Differentiation, Disease Models, Animal, Female, Humans, Regeneration, Spinal Cord Injuries, Rats, Sprague-Dawley, Cells, Immobilized, Hydrogels, Cell Proliferation, Rats, Neural Stem Cells, Cholinergic Neurons, Heterografts
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