Chondroitin sulfate glycosaminoglycan hydrogels create endogenous niches for neural stem cells
Abstract
Neural stem cells (NSCs) possess great potential for neural tissue repair after traumatic injuries to the central nervous system (CNS). However, poor survival and self-renewal of NSCs after injury severely limits its therapeutic potential. Sulfated chondroitin sulfate glycosaminoglycans (CS-GAGs) linked to CS proteoglycans (CSPGs) in the brain extracellular matrix (ECM) have the ability to bind and potentiate trophic factor efficacy, and promote NSC self-renewal in vivo. In this study, we investigated the potential of CS-GAG hydrogels composed of monosulfated CS-4 (CS-A), CS-6 (CS-C), and disulfated CS-4,6 (CS-E) CS-GAGs as NSC carriers, and their ability to create endogenous niches by enriching specific trophic factors to support NSC self-renewal. We demonstrate that CS-GAG hydrogel scaffolds showed minimal swelling and degradation over a period of 15 days in vitro, absorbing only 6.5 ± 0.019% of their initial weight, and showing no significant loss of mass during this period. Trophic factors FGF-2, BDNF, and IL10 bound with high affinity to CS-GAGs, and were significantly (p < 0.05) enriched in CS-GAG hydrogels when compared to unsulfated hyaluronic acid (HA) hydrogels. Dissociated rat subventricular zone (SVZ) NSCs when encapsulated in CS-GAG hydrogels demonstrated ∼88.5 ± 6.1% cell viability in vitro. Finally, rat neurospheres in CS-GAG hydrogels conditioned with the mitogen FGF-2 demonstrated significantly (p < 0.05) higher self-renewal when compared to neurospheres cultured in unconditioned hydrogels. Taken together, these findings demonstrate the ability of CS-GAG based hydrogels to regulate NSC self-renewal, and facilitate growth factor enrichment locally.
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Chondroitin sulfate proteoglycans bind neurotrophic factors such as FGF-2 and BDNF.
“Chondroitin sulfate proteoglycans bind neurotrophic factors such as FGF-2 and BDNF (Karumbaiah et al., 2015)”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Karumbaiah et al., 2015
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Chondroitin Sulfate Glycosaminoglycans for CNS Homeostasis-Implications for Material Design
Karumbaiah, L., Saxena, T. K., Betancur, M. I., & Bellamkonda, R. V. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666140815124447 · Cited by 9 · see citing works
Self-citation[Proteoglycans in the development, lesion, and aging of the brain].
Oohira, A. (2001) · PubMed · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Adult neurogenesis, glia, and the extracellular matrix
Cope, E. C., & Gould, E. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.03.023 · Cited by 236 · see citing works
Chondroitin sulfates and their binding molecules in the central nervous system
Djerbal, L., Lortat-Jacob, H., & Kwok, J. (2017) · Glycoconjugate Journal · doi:10.1007/s10719-017-9761-z · Cited by 144 · see citing works
Yamada, J., Nadanaka, S., Kitagawa, H., Takeuchi, K., & Jinno, S. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.0632-18.2018 · Cited by 38 · see citing works
- Authors
- Karumbaiah, L., Enam, S. F., Brown, A. C., Saxena, T., Betancur, M. I., Barker, T. H., & Bellamkonda, R. V.
- Affiliations
- University of Georgia (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Bellamkonda, Ravi V.
- ORCID
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-10-20
- Volume
- 26
- Issue
- 12
- Pages
- 2336-2349
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W2341520234
- Cited by
- 73
- References
- 101
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 12 · 2021: 8 · 2020: 11 · 2019: 11 · 2018: 4 · 2017: 8 · 2016: 5
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioconjugate Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Advancing Translational Sciences (UL1TR00454)
- Regenerative Engineering and Medicine Research Center
- National Center for Research Resources (1 P41 RR018502-01)
- National Institutes of Health (R01 079739)
- University of Georgia Athletic Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- neural stem cells, self-renewal, FGF2, brain-derived neurotrophic factor, IL-10, subventricular zone, neurospheres, central nervous system injury, extracellular matrix proteoglycans, hyaluronic acid hydrogel, cell encapsulation
- MeSH terms
- Animals, Cells, Cultured, Chondroitin Sulfates, Fibroblast Growth Factor 2, Brain-Derived Neurotrophic Factor, Hydrogels, Cell Proliferation, Rats, Tissue Scaffolds, Neural Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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