Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model
Abstract
Transplantation of pluripotent stem cells and their differentiated progeny has the potential to preserve or regenerate functional pathways and improve function after central nervous system injury. However, their utility has been hampered by poor survival and the potential to form tumors. Peptide-modified biomaterials influence cell adhesion, survival and differentiation in vitro, but their effectiveness in vivo remains uncertain. We synthesized a peptide-modified, minimally invasive, injectable hydrogel comprised of hyaluronan and methylcellulose to enhance the survival and differentiation of human induced pluripotent stem cell-derived oligodendrocyte progenitor cells. Cells were transplanted subacutely after a moderate clip compression rat spinal cord injury. The hydrogel, modified with the RGD peptide and platelet-derived growth factor (PDGF-A), promoted early survival and integration of grafted cells. However, prolific teratoma formation was evident when cells were transplanted in media at longer survival times, indicating that either this cell line or the way in which it was cultured is unsuitable for human use. Interestingly, teratoma formation was attenuated when cells were transplanted in the hydrogel, where most cells differentiated to a glial phenotype. Thus, this hydrogel promoted cell survival and integration, and attenuated teratoma formation by promoting cell differentiation.
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Hyaluronic acid and mixtures of hyaluronic acid and chitosan have been extensively used in the growth and construction of neural organoids.
“Similarly, hyaluronic acid and mixtures of hyaluronic acid and chitosan have been extensively used in the growth and construction of neural organoids111–116.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [111]
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- Authors
- Führmann, T., Tam, R. Y., Ballarin, B., Coles, B., Elliott Donaghue, I., van der Kooy, D., Nagy, A., Tator, C. H., Morshead, C. M., & Shoichet, M. S.
- Affiliations
- University of Toronto (CA)
- Mount Sinai Hospital (CA)
- Corresponding author
- Shoichet, M.S.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 83
- Pages
- 23-36
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2218149366
- Cited by
- 192
- References
- 72
- Citations by year
- 2026: 1 · 2025: 13 · 2024: 15 · 2023: 13 · 2022: 15 · 2021: 28 · 2020: 31 · 2019: 27 · 2018: 23 · 2017: 17 · 2016: 9
- FWCI
- 12.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- injectable hydrogel, oligodendrocyte precursor cells, spinal cord injury, teratoma formation, cell transplantation, RGD peptide, platelet-derived growth factor, hyaluronic acid, methylcellulose, cell survival, cell differentiation, glial phenotype, cell adhesion, rat model
- MeSH terms
- Animals, Behavior, Animal, Cattle, Cell Differentiation, Cell Movement, Cell Survival, Disease Models, Animal, Female, Flow Cytometry, Humans, Hyaluronic Acid, Injections, Methylcellulose, Oligodendroglia, Oligopeptides, Platelet-Derived Growth Factor, Spinal Cord Injuries, Teratoma, Rats, Sprague-Dawley, Cell Lineage, Hydrogel, Polyethylene Glycol Dimethacrylate, Induced Pluripotent Stem Cells
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