{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:22:41Z","timestamp":1760145761181,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hospital Nacional de Parapl\u00e9jicos de Toledo, Servicio de Salud de Castilla La Mancha"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic spinal cord injury (tSCI) has complex pathophysiological events that begin after the initial trauma. One such event is fibroglial scar formation by fibroblasts and reactive astrocytes. A strong inhibition of axonal growth is caused by the activated astroglial cells as a component of fibroglial scarring through the production of inhibitory molecules, such as chondroitin sulfate proteoglycans or myelin-associated proteins. Here, we used neural precursor cells (aldynoglia) as promoters of axonal growth and a fibrin hydrogel gelled under alkaline conditions to support and guide neuronal cell growth, respectively. We added Tol-51 sulfoglycolipid as a synthetic inhibitor of astrocyte and microglia in order to test its effect on the axonal growth-promoting function of aldynoglia precursor cells. We obtained an increase in GFAP expression corresponding to the expected glial phenotype for aldynoglia cells cultured in alkaline fibrin. In co-cultures of dorsal root ganglia (DRG) and aldynoglia, the axonal growth promotion of DRG neurons by aldynoglia was not affected. We observed that the neural precursor cells first clustered together and then formed niches from which aldynoglia cells grew and connected to groups of adjacent cells. We conclude that the combination of alkaline fibrin with synthetic sulfoglycolipid Tol-51 increased cell adhesion, cell migration, fasciculation, and axonal growth capacity, promoted by aldynoglia cells. There was no negative effect on the behavior of aldynoglia cells after the addition of sulfoglycolipid Tol-51, suggesting that a combination of aldynoglia plus alkaline fibrin and Tol-51 compound could be useful as a therapeutic strategy for tSCI repair.<\/jats:p>","DOI":"10.3390\/ijms25179173","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T05:16:24Z","timestamp":1724649384000},"page":"9173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Axonal Growth and Fasciculation of Spinal Neurons Promoted by Aldynoglia in Alkaline Fibrin Hydrogel: Influence of Tol-51 Sulfoglycolipid"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0880-9811","authenticated-orcid":false,"given":"Vinnitsa","family":"Buzoianu-Anguiano","sequence":"first","affiliation":[{"name":"Hospital Nacional de Parapl\u00e9jicos, Servicio de Salud de Castilla La Mancha, 45071 Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3875-6976","authenticated-orcid":false,"given":"Alejandro","family":"Arriero-Caba\u00f1ero","sequence":"additional","affiliation":[{"name":"Hospital Nacional de Parapl\u00e9jicos, Servicio de Salud de Castilla La Mancha, 45071 Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1241-7538","authenticated-orcid":false,"given":"Alfonso","family":"Fern\u00e1ndez-Mayoralas","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Bio-Org\u00e1nica, Instituto de Qu\u00edmica Org\u00e1nica General (IQOG-CSIC), CSIC, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mabel","family":"Torres-Llacsa","sequence":"additional","affiliation":[{"name":"Hospital Nacional de Parapl\u00e9jicos, Servicio de Salud de Castilla La Mancha, 45071 Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-9782","authenticated-orcid":false,"given":"Ernesto","family":"Doncel-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Hospital Nacional de Parapl\u00e9jicos, Servicio de Salud de Castilla La Mancha, 45071 Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","article-title":"Traumatic spinal cord injury","volume":"3","author":"Ahuja","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Buzoianu-Anguiano, V., Torres-Llacsa, M., and Doncel-P\u00e9rez, E. (2021). Role of Aldynoglia Cells in Neuroinflammatory and Neuroimmune Responses after Spinal Cord Injury. Cells, 10.","DOI":"10.3390\/cells10102783"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Garcia, E., Buzoianu-Anguiano, V., Silva-Garcia, R., Esparza-Salazar, F., Arriero-Caba\u00f1ero, A., Escandon, A., Doncel-P\u00e9rez, E., and Ibarra, A. (2023). Use of Cells, Supplements, and Peptides as Therapeutic Strategies for Modulating Inflammation after Spinal Cord Injury: An Update. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202307.2090.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.expneurol.2018.01.018","article-title":"Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats","volume":"306","author":"Sandner","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102935","DOI":"10.1016\/j.arcmed.2023.102935","article-title":"Traumatic Human Spinal Cord Injury: Are Single Treatments Enough to Solve the Problem?","volume":"55","year":"2024","journal-title":"Arch. Med. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/sc.2015.218","article-title":"The characteristics of posttraumatic syringomyelia","volume":"54","author":"Krebs","year":"2016","journal-title":"Spinal Cord"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Piejko, M., Jablonska, A., Walczak, P., and Janowski, M. (2019). Proteolytic Rafts for Improving Intraparenchymal Migration of Minimally Invasively Administered Hydrogel-Embedded Stem Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123083"},{"key":"ref_8","unstructured":"Verhaagen, J., and McDonald, J.W. (2012). Scaffolds to Promote Spinal Cord Regeneration. Handbook of Clinical Neurology, Elsevier."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.2147\/IJN.S124671","article-title":"A review of fibrin and fibrin composites for bone tissue engineering","volume":"12","author":"Noori","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1039\/C6IB00003G","article-title":"Dynamic behaviors of astrocytes in chemically modified fibrin and collagen hydrogels","volume":"8","author":"Seyedhassantehrani","year":"2016","journal-title":"Integr. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0079-6123(02)36026-6","article-title":"Chapter 24 CNS Schwann-like glia and functional restoration of damaged spinal cord","volume":"Volume 136","year":"2002","journal-title":"Progress in Brain Research"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/glia.20858","article-title":"Neurosphere cell differentiation to aldynoglia promoted by olfactory ensheathing cell conditioned medium","volume":"57","year":"2009","journal-title":"Glia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1002\/dvdy.21489","article-title":"Microarray analysis of striatal embryonic stem cells induced to differentiate by ensheathing cell conditioned media","volume":"237","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/(SICI)1098-1136(200003)30:1<49::AID-GLIA6>3.0.CO;2-M","article-title":"Schwann-like macroglia in adult rat brain","volume":"30","year":"2000","journal-title":"Glia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.4103\/1673-5374.187020","article-title":"Aldynoglia cells and modulation of RhoGTpase activity as useful tools for spinal cord injury repair","volume":"11","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.4103\/1673-5374.373674","article-title":"Axonal growth inhibitors and their receptors in spinal cord injury: From biology to clinical translation","volume":"18","author":"Chambel","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_17","first-page":"895","article-title":"Inhibition of glial proliferation, promotion of axonal growth and myelin production by synthetic glycolipid: A new approach for spinal cord injury treatment","volume":"33","year":"2015","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s10856-006-9837-y","article-title":"Gelation under dynamic conditions: A strategy for in vitro cell ordering","volume":"17","author":"Darder","year":"2006","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1021\/jm0611556","article-title":"Design and synthesis of glycoside inhibitors of glioma and melanoma growth","volume":"50","author":"Corrales","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Sierra, M., Garc\u00eda-\u00c1lvarez, I., Fern\u00e1ndez-Mayoralas, A., Moreno-Lillo, S., Barroso Garc\u00eda, G., Moral Dard\u00e9, V., and Doncel-P\u00e9rez, E. (2015). Mass spectrometry in pharmacokinetic studies of a synthetic compound for spinal cord injury treatment. Biomed Res. Int., 2015.","DOI":"10.1155\/2015\/169234"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10899","DOI":"10.1523\/JNEUROSCI.2269-10.2010","article-title":"Combined Genetic Attenuation of Myelin and Semaphorin-Mediated Growth Inhibition Is Insufficient to Promote Serotonergic Axon Regeneration","volume":"30","author":"Lee","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/brain\/awab317","article-title":"Inactivating Celsr2 promotes motor axon fasciculation and regeneration in mouse and human","volume":"145","author":"Wen","year":"2022","journal-title":"Brain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1242\/dev.048371","article-title":"Neuronal Nogo-A regulates neurite fasciculation, branching and extension in the developing nervous system","volume":"137","author":"Petrinovic","year":"2010","journal-title":"Development"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1093\/neuros\/nyw080","article-title":"Traumatic Spinal Cord Injury\u2014Repair and Regeneration","volume":"80","author":"Ahuja","year":"2017","journal-title":"Neurosurgery"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Fischer, G., B\u00e4ttig, L., Stienen, M.N., Curt, A., Fehlings, M.G., and Hejrati, N. (2024). Advancements in neuroregenerative and neuroprotective therapies for traumatic spinal cord injury. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1372920"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41393-022-00836-4","article-title":"Motor functional recovery efficacy of scaffolds with bone marrow stem cells in rat spinal cord injury: A Bayesian network meta-analysis","volume":"61","author":"Zhang","year":"2023","journal-title":"Spinal Cord"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1089\/neu.2008.0613","article-title":"Local Inhibition of Rho Signaling by Cell-Permeable Recombinant Protein BA-210 Prevents Secondary Damage and Promotes Functional Recovery following Acute Spinal Cord Injury","volume":"25","author":"Yang","year":"2008","journal-title":"J. Neurotrauma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e3062","DOI":"10.1002\/jgm.3062","article-title":"HIF-1\u03b1 promotes bone marrow stromal cell migration to the injury site and enhances functional recovery after spinal cord injury in rats","volume":"20","author":"Han","year":"2018","journal-title":"J. Gene Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"025004","DOI":"10.1088\/1741-2552\/aaa55c","article-title":"Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury","volume":"15","author":"Geissler","year":"2018","journal-title":"J. Neural Eng."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neuroscience.2023.08.034","article-title":"Role of Axon Guidance Molecules in Ascending and Descending Paths in Spinal Cord Regeneration","volume":"533","author":"Vartak","year":"2023","journal-title":"Neuroscience"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3171\/2019.8.SPINE19201","article-title":"A combination of mesenchymal stem cells and scaffolds promotes motor functional recovery in spinal cord injury: A systematic review and meta-analysis","volume":"32","author":"Yousefifard","year":"2020","journal-title":"J. Neurosurg. Spine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00281-011-0290-8","article-title":"Fibrinogen as a key regulator of inflammation in disease","volume":"34","author":"Davalos","year":"2012","journal-title":"Semin. Immunopathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13410","DOI":"10.1074\/jbc.M112.426254","article-title":"Extracellular Acidosis Is a Novel Danger Signal Alerting Innate Immunity via the NLRP3 Inflammasome","volume":"288","author":"Nurmi","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.actbio.2017.04.010","article-title":"Prompt peripheral nerve regeneration induced by a hierarchically aligned fibrin nanofiber hydrogel","volume":"55","author":"Du","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.neuint.2010.12.024","article-title":"Regulation of adult neural precursor cell migration","volume":"59","author":"Leong","year":"2011","journal-title":"Neurochem. Int."},{"key":"ref_36","first-page":"181","article-title":"Astrocytes as neural stem cells in the adult brain","volume":"7","year":"2012","journal-title":"J. Stem Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12974-020-01814-4","article-title":"Anti-IL-20 antibody improved motor function and reduced glial scar formation after traumatic spinal cord injury in rats","volume":"17","author":"Lee","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s00701-023-05520-x","article-title":"Glial fibrillary acidic protein is a robust biomarker in cerebrospinal fluid and peripheral blood after traumatic spinal cord injury: A prospective pilot study","volume":"165","author":"Wichmann","year":"2023","journal-title":"Acta Neurochir."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"146547","DOI":"10.1016\/j.brainres.2019.146547","article-title":"Blood-brain barrier leakage of blood proteins in idiopathic normal pressure hydrocephalus","volume":"1727","author":"Eide","year":"2020","journal-title":"Brain Res."},{"key":"ref_40","unstructured":"Colman DR, F.M. (1999). Cell Adhesion Molecules and Axonal Outgrowth. Basic Neurochemistry: Molecular, Cellular and Medical Aspects, Raven Press. [6th ed.]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1523\/JNEUROSCI.20-11-04177.2000","article-title":"A MAP Kinase-Signaling Pathway Mediates Neurite Outgrowth on L1 and Requires Src-Dependent Endocytosis","volume":"20","author":"Schmid","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1007\/s12031-014-0436-y","article-title":"Neural Cell Adhesion Molecule NrCAM Is Expressed in the Mammalian Inner Ear and Modulates Spiral Ganglion Neurite Outgrowth in an In Vitro Alternate Choice Assay","volume":"55","author":"Brand","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jneuroim.2010.02.002","article-title":"Strain-specific BDNF expression of rat primary astrocytes","volume":"220","author":"Wei","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13064-020-0138-9","article-title":"Evaluating the effectiveness of anti-Nogo treatment in spinal cord injuries","volume":"15","author":"Mohammed","year":"2020","journal-title":"Neural Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1177\/002215540305100111","article-title":"Cellular Characterization of Epidermal Growth Factor-expanded Free-floating Neurospheres","volume":"51","author":"Lobo","year":"2003","journal-title":"J. Histochem. Cytochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9173\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:30Z","timestamp":1760110950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,23]]},"references-count":46,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179173"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179173","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,8,23]]}}}