The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
A Sensitive and Reliable Locomotor Rating Scale for Open Field Testing in Rats
BASSO, D. M., BEATTIE, M. S., & BRESNAHAN, J. C. (1995) · Journal of Neurotrauma · doi:10.1089/neu.1995.12.1 · Cited by 3,963
CD44: From adhesion molecules to signalling regulators
Ponta, H., Sherman, L. S., & Herrlich, P. A. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1004 · Cited by 2,458
piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells
Woltjen, K., Michael, I. P., Mohseni, P., Desai, R., Mileikovsky, M., Hämäläinen, R. H., Cowling, R. A., Wang, W., Liu, P., Gertsenstein, M., et al. (2009) · Nature · doi:10.1038/nature07863 · Cited by 1,810
Self-citationM2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,777
Keirstead, H. S., Nistor, G., Bernal, G. M., Totoiu, M. O., Cloutier, F., Sharp, K. L., & Steward, O. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0311-05.2005 · Cited by 1,263
Frisch, S. M., & Screaton, R. A. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00251-9 · Cited by 1,249
Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants
Brüstle, O., Jones, K. N., Learish, R. D., Karram, K., Choudhary, K., Wiestler, O. D., Duncan, I. D., & McKay, R. D. G. (1999) · Science · doi:10.1126/science.285.5428.754 · Cited by 976
A photolabile hydrogel for guided three-dimensional cell growth and migration
Luo, Y., & Shoichet, M. S. (2004) · Nature Materials · doi:10.1038/nmat1092 · Cited by 801
Self-citationMacrophage activation and its role in repair and pathology after spinal cord injury
Gensel, J. C., & Zhang, B. (2015) · Brain Research · doi:10.1016/j.brainres.2014.12.045 · Cited by 792
Direct Neural Fate Specification from Embryonic Stem Cells
Tropepe, V., Hitoshi, S., Sirard, C., Mak, T. W., Rossant, J., & van der Kooy, D. (2001) · Neuron · doi:10.1016/s0896-6273(01)00263-x · Cited by 757
Advantages of RGD peptides for directing cell association with biomaterials
Bellis, S. L. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.02.029 · Cited by 746
A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury
Tetzlaff, W., Okon, E. B., Karimi‐Abdolrezaee, S., Hill, C. E., Sparling, J. S., Plemel, J. R., Plunet, W. T., Tsai, E. C., Baptiste, D. C., Smithson, L. J., et al. (2010) · Journal of Neurotrauma · doi:10.1089/neu.2009.1177 · Cited by 596
Wang, S., Bates, J., Li, X., Schanz, S., Chandler-Militello, D., Levine, C., Maherali, N., Studer, L., Hochedlinger, K., Windrem, M., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2012.12.002 · Cited by 586
Nistor, G. I., Totoiu, M. O., Haque, N. S. K., Carpenter, M. K., & Keirstead, H. S. (2004) · Glia · doi:10.1002/glia.20127 · Cited by 582
Nori, S., Okada, Y., Yasuda, A., Tsuji, O., Takahashi, Y., Kobayashi, Y., Fujiyoshi, K., Koike, M., Uchiyama, Y., Ikeda, E., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108077108 · Cited by 546
Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat.
Rivlin, A. S., & Tator, C. H. (1978) · PubMed · Cited by 495
Self-citationTang, C. Z., Lee, A. S., Volkmer, J.-P., Sahoo, D., Nag, D., Mosley, A. R., Inlay, M. A., Ardehali, R., Chavez, S. L., Pera, R. A. R., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1947 · Cited by 376
Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach
Tam, R. Y., Führmann, T., Mitrousis, N., & Shoichet, M. S. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.237 · Cited by 296
Self-citationSelective Ablation of Human Embryonic Stem Cells Expressing a “Suicide” Gene
Schuldiner, M., Itskovitz‐Eldor, J., & Benvenisty, N. (2003) · Stem Cells · doi:10.1634/stemcells.21-3-257 · Cited by 287
Differentiation of human oligodendrocytes from pluripotent stem cells
Hu, B., Du, Z., & Zhang, S. (2009) · Nature Protocols · doi:10.1038/nprot.2009.186 · Cited by 260
Mothe, A. J., Tam, R. Y., Zahir, T., Tator, C. H., & Shoichet, M. S. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.02.002 · Cited by 254
Self-citationA hydrogel-based stem cell delivery system to treat retinal degenerative diseases
Ballios, B. G., Cooke, M. J., van der Kooy, D., & Shoichet, M. S. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2009.12.004 · Cited by 250
Self-citationInhibition of pluripotent stem cell-derived teratoma formation by small molecules
Lee, M.-O., Moon, S. H., Jeong, H.-C., Yi, J.-Y., Lee, T.-H., Shim, S. H., Rhee, Y.-H., Lee, S.-H., Oh, S.-J., Lee, M.-Y., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303669110 · Cited by 246 · cited 3×
“Many conceptually different strategies to block teratoma formation have been pursued, including the introduction of suicide genes [4,5], selection of the desired cell type to increase purity [6], immunodepletion [7], cytotoxic antibodies [8] and selective ablation of pluripotent cells with small molecules [9].”
BackgroundEmbryonic stem cells assume a primitive neural stem cell fate in the absence of extrinsic influences
Smukler, S. R., Runciman, S. B., Xu, S., & van der Kooy, D. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200508085 · Cited by 246
Choo, A. B. H., Tan, H. L., Ang, S. N., Fong, W. J., Chin, A. C. P., Lo, J. C. Y., Zheng, L., Hentze, H., Philp, R. J., Oh, S., et al. (2008) · Stem Cells · doi:10.1634/stemcells.2007-0576 · Cited by 244
Ballios, B. G., Cooke, M. J., Donaldson, L., Coles, B. L. K., Morshead, C. M., van der Kooy, D., & Shoichet, M. S. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.04.008 · Cited by 228
Self-citationZhang, S., Ge, B., & Duncan, I. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.4089 · Cited by 217
CD44 expression identifies astrocyte-restricted precursor cells
Liu, Y., Han, S. S. W., Wu, Y., Tuohy, T. M. F., Xue, H., Cai, J., Back, S. A., Sherman, L. S., Fischer, I., & Rao, M. S. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.08.018 · Cited by 215
Cell transplantation therapies for spinal cord injury focusing on induced pluripotent stem cells
Nakamura, M., & Okano, H. (2013) · Cell Research · doi:10.1038/cr.2012.171 · Cited by 214
Gudz, T. I., Komuro, H., & Macklin, W. B. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4054-05.2006 · Cited by 213
Sim, F. J., McClain, C. R., Schanz, S. J., Protack, T. L., Windrem, M. S., & Goldman, S. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1972 · Cited by 208
Non-specific binding of antibodies in immunohistochemistry: fallacies and facts
Buchwalow, I., Samoilova, V. E., Boecker, W., & Tiemann, M. (2011) · Scientific Reports · doi:10.1038/srep00028 · Cited by 196
High Efficacy of Clonal Growth and Expansion of Adult Neural Stem Cells
Wachs, F., Couillard‐Després, S., Engelhardt, M., Wilhelm, D., Ploetz, S., Vroemen, M., Kaesbauer, J., Uyanik, G., Klucken, J., Karl, C., et al. (2003) · Laboratory Investigation · doi:10.1097/01.lab.0000075556.74231.a5 · Cited by 188
The role of ECM proteins and protein fragments in guiding cell behavior in regenerative medicine
Barker, T. H. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.02.027 · Cited by 181
Hu, B.-Y., Du, Z.-W., Li, X.-J., Ayala, M., & Zhang, S.-C. (2009) · Development · doi:10.1242/dev.029447 · Cited by 169
Peptide surface modification of methacrylamide chitosan for neural tissue engineering applications
Yu, L. M. Y., Kazazian, K., & Shoichet, M. S. (2007) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31069 · Cited by 169
Self-citationPreconditioning Stem Cells for In Vivo Delivery
Sart, S., Ma, T., & Li, Y. (2014) · BioResearch open access · doi:10.1089/biores.2014.0012 · Cited by 166
Salewski, R. P., Mitchell, A., Li, L., Shen, C., Milekovskaia, M., Nagy, A., & Fehlings, M. G. (2015) · Stem Cells Translational Medicine · doi:10.5966/sctm.2014-0236 · Cited by 165
Self-citationChronic Oligodendrogenesis and Remyelination after Spinal Cord Injury in Mice and Rats
Hesp, Z. C., Goldstein, E. A., Miranda, C. J., Kaspar, B. K., & McTigue, D. M. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2568-14.2015 · Cited by 164
Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke
Wang, Y., Cooke, M. J., Sachewsky, N., Morshead, C. M., & Shoichet, M. S. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.07.032 · Cited by 145
Self-citationChung, S., Shin, B., Hedlund, E., Pruszak, J., Ferree, A. W., Kang, U. J., Ole Isacson, A., & Kim, K. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03841.x · Cited by 142
Yang, C., Przyborski, S., Cooke, M. J., Zhang, X., Stewart, R., Anyfantis, G., Atkinson, S. P., Saretzki, G., Armstrong, L., & Lako, M. (2008) · Stem Cells · doi:10.1634/stemcells.2007-0677 · Cited by 136
Clip Compression Model Is Useful for Thoracic Spinal Cord Injuries
Poon, P. C., Gupta, D., Shoichet, M. S., & Tator, C. H. (2007) · Spine · doi:10.1097/brs.0b013e31815b7e6b · Cited by 131
Self-citationKang, C. E., Poon, P. C., Tator, C. H., & Shoichet, M. S. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2007.0349 · Cited by 124
Self-citationDressel, R., Schindehütte, J., Kuhlmann, T., Elsner, L., Novota, P., Baier, P. C., Schillert, A., Bickeböller, H., Herrmann, T., Trenkwalder, C., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002622 · Cited by 118
Austin, J. W., Kang, C. E., Baumann, M. D., DiDiodato, L., Satkunendrarajah, K., Wilson, J. R., Stanisz, G. J., Shoichet, M. S., & Fehlings, M. G. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.03.022 · Cited by 114
Self-citationTam, R. Y., Cooke, M. J., & Shoichet, M. S. (2012) · Journal of Materials Chemistry · doi:10.1039/c2jm33680d · Cited by 99
Self-citationAizawa, Y., Leipzig, N. D., Zahir, T., & Shoichet, M. S. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.08.018 · Cited by 89
Self-citationConcept and progress in the development of RGD‐containing peptide pharmaceuticals
Craig, W. S., Cheng, S., Mullen, D. G., Blevitt, J., & Pierschbacher, M. D. (1995) · Biopolymers · doi:10.1002/bip.360370209 · Cited by 86
Anderson, A. J., Haus, D. L., Hooshmand, M. J., Perez, H. D., Sontag, C. J., & Cummings, B. J. (2011) · Regenerative Medicine · doi:10.2217/rme.11.22 · Cited by 84
Hydrogel/electrospun fiber composites influence neural stem/progenitor cell fate
Hsieh, A., Zahir, T., Lapitsky, Y., Amsden, B. G., Wan, W., & Shoichet, M. S. (2010) · Soft Matter · doi:10.1039/b924349f · Cited by 77
Self-citationHu, J., Deng, L., Wang, X., & Xu, X. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22111 · Cited by 68
Wrongful Termination: Lessons From the Geron Clinical Trial
Scott, C. T., & Magnus, D. C. (2014) · Stem Cells Translational Medicine · doi:10.5966/sctm.2014-0147 · Cited by 66
CERVICAL SPINAL CORD THERAPEUTICS DELIVERY
Riley, J. P., Federici, T., Park, J. B., Suzuki, M., Franz, C. K., Tork, C. A., McHugh, J., Teng, Q., Svendsen, C. N., & Boulis, N. M. (2009) · Neurosurgery · doi:10.1227/01.neu.0000343524.45387.9e · Cited by 63
Cooke, M. J., Zahir, T., Phillips, S. R., Shah, D. S. H., Athey, D., Lakey, J. H., Shoichet, M. S., & Przyborski, S. A. (2009) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32585 · Cited by 59
Self-citationEmerging Concepts in Engineering Extracellular Matrix Variants for Directing Cell Phenotype
Brown, A. C., & Barker, T. H. (2009) · Regenerative Medicine · doi:10.2217/rme.09.30 · Cited by 59
A Scalable Approach to Prevent Teratoma Formation of Human Embryonic Stem Cells
Rong, Z., Fu, X., Wang, M., & Xu, Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.383810 · Cited by 58
Novel intrathecal delivery system for treatment of spinal cord injury
Hamann, M. C. J., Tsai, E. C., Tator, C. H., & Shoichet, M. S. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00040-2 · Cited by 58
Self-citationTransportin Regulates Nuclear Import of CD44
Janiszewska, M., Vito, C. D., Bitoux, M. L., Fusco, C., & Stamenkovic, I. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.075838 · Cited by 54
Turaç, G., Hindley, C. J., Thomas, R., Davis, J. A., Deleidi, M., Gasser, T., Karaöz, E., & Pruszak, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068519 · Cited by 48
Weible, M. W., & Chan‐Ling, T. (2007) · Glia · doi:10.1002/glia.20539 · Cited by 48
Pfeifer, K., Vroemen, M., Caioni, M., Aigner, L., Bogdahn, U., & Weidner, N. (2006) · Regenerative Medicine · doi:10.2217/17460751.1.2.255 · Cited by 47
Crang, A. J., Gilson, J. M., & Blakemore, W. F. (1998) · Journal of Neurocytology · doi:10.1023/a:1006960032023 · Cited by 46
Clonal Neural Stem Cells from Human Embryonic Stem Cell Colonies
Chaddah, R., Arntfield, M. E., Runciman, S. I. C., Clarke, L., & van der Kooy, D. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3286-11.2012 · Cited by 46
Chan, L. Y., Yim, E. K. F., & Choo, A. B. H. (2012) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2012.0150 · Cited by 42
Vadivelu, S., Stewart, T. J., Qu, Y., Horn, K. P., Liu, S., Li, Q., Silver, J., & McDonald, J. W. (2015) · Stem Cells Translational Medicine · doi:10.5966/sctm.2014-0107 · Cited by 40
Effects of implantation site of dead stem cells in rats with stroke damage
Modo, M., Stroemer, R. P., Tang, E., Patel, S., & Hodges, H. M. (2003) · Neuroreport · doi:10.1097/00001756-200301200-00007 · Cited by 37
Weinger, J. G., Weist, B. M., Plaisted, W. C., Klaus, S. M., Walsh, C. M., & Lane, T. E. (2012) · Stem Cells · doi:10.1002/stem.1234 · Cited by 27
Kawa, A., Stahlhut, M., Berezin, A. Е., Bock, E., & Berezin, V. (1998) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(97)00165-9 · Cited by 26
Führmann, T., Gerardo‐Nava, J., & Brook, G. A. (2010) · Springer eBooks · doi:10.1007/978-3-642-02824-3_12 · Cited by 14
Self-citationDu, Q., Guan, Y., Ji, H., Chen, Z., & Zhang, Y. A. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.09.048 · Cited by 2
Guan, Y., Du, Q., Zhu, W., Zou, C., Wu, D., Chen, L., & Zhang, Y. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054332 · Cited by 2
Flagged first, then by citations
Cited by
Sorted by citations
Self-Healing Injectable Hydrogels for Tissue Regeneration
Bertsch, P., Diba, M., Mooney, D. J., & Leeuwenburgh, S. C. G. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00179 · Cited by 943
Supramolecular Adhesive Hydrogels for Tissue Engineering Applications
Zhao, Y., Song, S., Ren, X., Zhang, J., Lin, Q., & Zhao, Y. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00815 · Cited by 714
Shattering barriers toward clinically meaningful MSC therapies
Levy, O., Kuai, R., Siren, E. M. J., Bhere, D., Milton, Y., Nissar, N., De Biasio, M., Heinelt, M., Reeve, B., Abdi, R., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba6884 · Cited by 694
Bioengineering strategies to accelerate stem cell therapeutics
Madl, C. M., Heilshorn, S. C., & Blau, H. M. (2018) · Nature · doi:10.1038/s41586-018-0089-z · Cited by 434
Towards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409
Metadata
- 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
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Clinical Neurology › 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
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
