Cited by 73Hydrogels: synthesis, properties, applicationsProteoglycans and glycosaminoglycans researchNeurogenesis and neuroplasticity mechanisms

Chondroitin sulfate glycosaminoglycan hydrogels create endogenous niches for neural stem cells

Karumbaiah, Lohitash, Enam, Syed Faaiz, Brown, Ashley C., Saxena, Tarun, Betancur, Martha I., Barker, Thomas H., Bellamkonda, Ravi V.·2015·Bioconjugate Chemistry

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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Crossref · 10.1021/acs.bioconjchem.5b00397

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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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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.
Venue
Bioconjugate Chemistry
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

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