{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T15:20:58Z","timestamp":1769354458389,"version":"3.49.0"},"reference-count":100,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Youth and Sports Czech Republic","award":["CZ.02.1.01\/0.0.\/0.0\/15_003\/0000419"],"award-info":[{"award-number":["CZ.02.1.01\/0.0.\/0.0\/15_003\/0000419"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal cord injury is a devastating medical condition with no effective treatment. One approach to SCI treatment may be provided by stem cells (SCs). Studies have mainly focused on the transplantation of exogenous SCs, but the induction of endogenous SCs has also been considered as an alternative. While the differentiation potential of neural stem cells in the brain neurogenic regions has been known for decades, there are ongoing debates regarding the multipotent differentiation potential of the ependymal cells of the central canal in the spinal cord (SCECs). Following spinal cord insult, SCECs start to proliferate and differentiate mostly into astrocytes and partly into oligodendrocytes, but not into neurons. However, there are several approaches concerning how to increase neurogenesis in the injured spinal cord, which are discussed in this review. The potential treatment approaches include drug administration, the reduction of neuroinflammation, neuromodulation with physical factors and in vivo reprogramming.<\/jats:p>","DOI":"10.3390\/ijms23073728","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:44:52Z","timestamp":1648590292000},"page":"3728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Neurogenesis as a Tool for Spinal Cord Injury"],"prefix":"10.3390","volume":"23","author":[{"given":"Katerina","family":"Havelikova","sequence":"first","affiliation":[{"name":"Institute of Experimental Medicine, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14220 Prague, Czech Republic"},{"name":"Department of Neuroscience, Second Faculty of Medicine, Charles University, 15006 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4812-9458","authenticated-orcid":false,"given":"Barbora","family":"Smejkalova","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14220 Prague, Czech Republic"},{"name":"Department of Neuroscience, Second Faculty of Medicine, Charles University, 15006 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4644-9212","authenticated-orcid":false,"given":"Pavla","family":"Jendelova","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14220 Prague, Czech Republic"},{"name":"Department of Neuroscience, Second Faculty of Medicine, Charles University, 15006 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rowland, J.W., Hawryluk, G.W., Kwon, B., and Fehlings, M.G. (2008). Current status of acute spinal cord injury pathophysiology and emerging therapies: Promise on the horizon. Neurosurg. Focus, 25.","DOI":"10.3171\/FOC.2008.25.11.E2"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ahuja, C.S., Wilson, J.R., Nori, S., Kotter, M.R.N., Druschel, C., Curt, A., and Fehlings, M.G. (2017). Traumatic spinal cord injury. Nat. Rev. Dis. Primers, 3.","DOI":"10.1038\/nrdp.2017.18"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00441-019-03039-1","article-title":"Spinal cord injury: Pathophysiology, treatment strategies, associated challenges, and future implications","volume":"377","author":"Venkatesh","year":"2019","journal-title":"Cell Tissue Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/jnr.22602","article-title":"Ion channel blockers and spinal cord injury","volume":"89","author":"Liu","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1007S","DOI":"10.1093\/jn\/130.4.1007S","article-title":"Glutamate as a neurotransmitter in the brain: Review of physiology and pathology","volume":"130","author":"Meldrum","year":"2000","journal-title":"J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/sc.2011.111","article-title":"Oxidative stress in spinal cord injury and antioxidant-based intervention","volume":"50","author":"Jia","year":"2012","journal-title":"Spinal Cord"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Christie, S.D., Comeau, B., Myers, T., Sadi, D., Purdy, M., and Mendez, I. (2008). Duration of lipid peroxidation after acute spinal cord injury in rats and the effect of methylprednisolone. Neurosurg. Focus, 25.","DOI":"10.3171\/FOC.2008.25.11.E5"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liu, S., Sarkar, C., Dinizo, M., Faden, A.I., Koh, E.Y., Lipinski, M.M., and Wu, J. (2015). Disrupted autophagy after spinal cord injury is associated with er stress and neuronal cell death. Cell Death Dis., 6.","DOI":"10.1038\/cddis.2014.527"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0079-6123(06)61011-X","article-title":"Traumatic injury of the spinal cord and nitric oxide","volume":"161","author":"Marsala","year":"2007","journal-title":"Prog. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.1038\/s41467-019-11707-7","article-title":"Moving beyond the glial scar for spinal cord repair","volume":"10","author":"Bradbury","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.cmet.2020.02.002","article-title":"Restoring cellular energetics promotes axonal regeneration and functional recovery after spinal cord injury","volume":"31","author":"Han","year":"2020","journal-title":"Cell Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0079-6123(02)37006-7","article-title":"Cell death in models of spinal cord injury","volume":"137","author":"Beattie","year":"2002","journal-title":"Prog. Brain Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"281","DOI":"10.55782\/ane-2011-1848","article-title":"Secondary injury mechanisms in traumatic spinal cord injury: A nugget of this multiply cascade","volume":"71","author":"Oyinbo","year":"2011","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.3390\/molecules20033527","article-title":"Glycosaminoglycans and glycomimetics in the central nervous system","volume":"20","author":"Rowlands","year":"2015","journal-title":"Molecules"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Leal-Galicia, P., Chavez-Hernandez, M.E., Mata, F., Mata-Luevanos, J., Rodriguez-Serrano, L.M., Tapia-de-Jesus, A., and Buenrostro-Jauregui, M.H. (2021). Adult neurogenesis: A story ranging from controversial new neurogenic areas and human adult neurogenesis to molecular regulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111489"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bergmann, O., Spalding, K.L., and Frisen, J. (2015). Adult neurogenesis in humans. Cold Spring Harb. Perspect. Biol., 7.","DOI":"10.1101\/cshperspect.a018994"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s11011-021-00864-8","article-title":"Adult human neurogenesis: Early studies clarify recent controversies and go further","volume":"37","author":"Nogueira","year":"2022","journal-title":"Metab. Brain Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.stem.2010.07.014","article-title":"Origin of new glial cells in intact and injured adult spinal cord","volume":"7","author":"Goritz","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1097\/00005072-196210000-00007","article-title":"Incorporation of thymidine-h3 by cells in normal and injured mouse spinal cord","volume":"21","author":"Adrian","year":"1962","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1523\/JNEUROSCI.20-06-02218.2000","article-title":"Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord","volume":"20","author":"Horner","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Meletis, K., Barnabe-Heider, F., Carlen, M., Evergren, E., Tomilin, N., Shupliakov, O., and Frisen, J. (2008). Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol., 6.","DOI":"10.1371\/journal.pbio.0060182"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7599","DOI":"10.1523\/JNEUROSCI.16-23-07599.1996","article-title":"Multipotent cns stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis","volume":"16","author":"Weiss","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Maeda, Y., Nakagomi, N., Nakano-Doi, A., Ishikawa, H., Tatsumi, Y., Bando, Y., Yoshikawa, H., Matsuyama, T., Gomi, F., and Nakagomi, T. (2019). Potential of adult endogenous neural stem\/progenitor cells in the spinal cord to contribute to remyelination in experimental autoimmune encephalomyelitis. Cells, 8.","DOI":"10.3390\/cells8091025"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000369466","article-title":"An astrocyte regenerative response from vimentin-containing cells in the spinal cord of amyotrophic lateral sclerosis\u2019s disease-like transgenic (g93a sod1) mice","volume":"15","author":"Zhou","year":"2015","journal-title":"Neurodegener. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s10571-009-9387-1","article-title":"Response of ependymal progenitors to spinal cord injury or enhanced physical activity in adult rat","volume":"29","author":"Cizkova","year":"2009","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_26","first-page":"3835","article-title":"Endogenous neural stem cells in central canal of adult rats acquired limited ability to differentiate into neurons following mild spinal cord injury","volume":"8","author":"Liu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1523\/JNEUROSCI.4070-05.2005","article-title":"Endogenous neurogenesis replaces oligodendrocytes and astrocytes after primate spinal cord injury","volume":"26","author":"Yang","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive astrocyte nomenclature, definitions, and future directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.nurt.2010.07.003","article-title":"Reactive astrocytes as therapeutic targets for cns disorders","volume":"7","author":"Hamby","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1126\/science.1242576","article-title":"Resident neural stem cells restrict tissue damage and neuronal loss after spinal cord injury in mice","volume":"342","author":"Sabelstrom","year":"2013","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1089\/scd.2011.0242","article-title":"In vitro characterization of trophic factor expression in neural precursor cells","volume":"21","author":"Hawryluk","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nn1405","article-title":"Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome","volume":"8","author":"Hofstetter","year":"2005","journal-title":"Nat. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8727","DOI":"10.1523\/JNEUROSCI.20-23-08727.2000","article-title":"Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus","volume":"20","author":"Shihabuddin","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1172\/JCI42957","article-title":"Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury","volume":"120","author":"Abematsu","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.brainres.2014.11.029","article-title":"In vitro characteristics of valproic acid and all-trans-retinoic acid and their combined use in promoting neuronal differentiation while suppressing astrocytic differentiation in neural stem cells","volume":"1596","author":"Chu","year":"2015","journal-title":"Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1007\/s11064-015-1618-x","article-title":"Valproic acid arrests proliferation but promotes neuronal differentiation of adult spinal nspcs from sci rats","volume":"40","author":"Chu","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.tibs.2003.12.004","article-title":"The glamour and gloom of glycogen synthase kinase-3","volume":"29","author":"Jope","year":"2004","journal-title":"Trends Biochem. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1254\/jphs.CR0070024","article-title":"The wnt\/beta-catenin signaling pathway as a target in drug discovery","volume":"104","author":"Sasaguri","year":"2007","journal-title":"J. Pharmacol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1124\/pr.111.005512","article-title":"Therapeutic potential of mood stabilizers lithium and valproic acid: Beyond bipolar disorder","volume":"65","author":"Chiu","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref_40","first-page":"37","article-title":"Valproic acid, a molecular lead to multiple regulatory pathways","volume":"53","author":"Kostrouchova","year":"2007","journal-title":"Folia Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2217\/rme.14.86","article-title":"Valproic acid-mediated neuroprotection and neurogenesis after spinal cord injury: From mechanism to clinical potential","volume":"10","author":"Chu","year":"2015","journal-title":"Regen. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s13311-020-00928-0","article-title":"Activation of neurogenesis in multipotent stem cells cultured in vitro and in the spinal cord tissue after severe injury by inhibition of glycogen synthase kinase-3","volume":"18","author":"Vilches","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.biocel.2017.05.030","article-title":"Substance p enhances endogenous neurogenesis to improve functional recovery after spinal cord injury","volume":"89","author":"Yang","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4174","DOI":"10.1038\/s41598-017-04528-5","article-title":"Inhibition of erk1\/2 restores gsk3beta activity and protein synthesis levels in a model of tuberous sclerosis","volume":"7","author":"Pal","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/sj.onc.1209004","article-title":"Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase","volume":"25","author":"Wang","year":"2006","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.3892\/or.2015.4111","article-title":"Erk\/gsk3beta signaling is involved in atractylenolide i-induced apoptosis and cell cycle arrest in melanoma cells","volume":"34","author":"Ye","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_47","first-page":"8129","article-title":"Retinoic acid induced the differentiation of neural stem cells from embryonic spinal cord into functional neurons in vitro","volume":"8","author":"Tan","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neulet.2018.10.002","article-title":"Combined use of bfgf\/egf and all-trans-retinoic acid cooperatively promotes neuronal differentiation and neurite outgrowth in neural stem cells","volume":"690","author":"Zhao","year":"2019","journal-title":"Neurosci. Lett"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fnana.2017.00094","article-title":"The baf45d protein is preferentially expressed in adult neurogenic zones and in neurons and may be required for retinoid acid induced pax6 expression","volume":"11","author":"Liu","year":"2017","journal-title":"Front. Neuroanat."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.3389\/fnins.2019.01151","article-title":"Baf45d downregulation in spinal cord ependymal cells following spinal cord injury in adult rats and its potential role in the development of neuronal lesions","volume":"13","author":"Wang","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1523\/JNEUROSCI.2056-19.2020","article-title":"Connexin signaling is involved in the reactivation of a latent stem cell niche after spinal cord injury","volume":"40","author":"Fabbiani","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00441-016-2421-y","article-title":"Connexin 50 modulates sox2 expression in spinal-cord-derived ependymal stem\/progenitor cells","volume":"365","author":"Alastrue","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1038\/ncomms4338","article-title":"In vivo conversion of astrocytes to neurons in the injured adult spinal cord","volume":"5","author":"Su","year":"2014","journal-title":"Nat Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.amjms.2016.10.009","article-title":"Erythropoietin and nonhematopoietic effects","volume":"353","author":"Nekoui","year":"2017","journal-title":"Am. J. Med. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.jvs.2015.10.011","article-title":"Erythropoietin preconditioning improves clinical and histologic outcome in an acute spinal cord ischemia and reperfusion rabbit model","volume":"64","author":"Simon","year":"2016","journal-title":"J. Vasc Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1038\/mp.2015.212","article-title":"Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus","volume":"21","author":"Hassouna","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_57","first-page":"264","article-title":"Erythropoietin signaling increases neurogenesis and oligodendrogenesis of endogenous neural stem cells following spinal cord injury both in vivo and in vitro","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Keefe, K.M., Sheikh, I.S., and Smith, G.M. (2017). Targeting neurotrophins to specific populations of neurons: Ngf, bdnf, and nt-3 and their relevance for treatment of spinal cord injury. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030548"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41419-020-2620-z","article-title":"Strategies and prospects of effective neural circuits reconstruction after spinal cord injury","volume":"11","author":"Yang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kanakasabai, S., Pestereva, E., Chearwae, W., Gupta, S.K., Ansari, S., and Bright, J.J. (2012). Ppargamma agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050500"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.expneurol.2005.01.030","article-title":"Injectable intrathecal delivery system for localized administration of egf and fgf-2 to the injured rat spinal cord","volume":"194","author":"Tator","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/jnen\/59.8.687","article-title":"Epidermal growth factor and fibroblast growth factor 2 cause proliferation of ependymal precursor cells in the adult rat spinal cord in vivo","volume":"59","author":"Kojima","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1089\/08977150252806974","article-title":"Intrathecal administration of epidermal growth factor and fibroblast growth factor 2 promotes ependymal proliferation and functional recovery after spinal cord injury in adult rats","volume":"19","author":"Kojima","year":"2002","journal-title":"J. Neurotrauma"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11948","DOI":"10.1523\/JNEUROSCI.3127-06.2006","article-title":"Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord","volume":"26","author":"Ohori","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.expneurol.2018.11.003","article-title":"Validation study of neurotrophin-3-releasing chitosan facilitation of neural tissue generation in the severely injured adult rat spinal cord","volume":"312","author":"Oudega","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"13354","DOI":"10.1073\/pnas.1510194112","article-title":"Nt3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury","volume":"112","author":"Yang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"E5595","DOI":"10.1073\/pnas.1804735115","article-title":"Nt3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury","volume":"115","author":"Rao","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s11427-017-9217-2","article-title":"Application of the sodium hyaluronate-cntf scaffolds in repairing adult rat spinal cord injury and facilitating neural network formation","volume":"61","author":"Xie","year":"2018","journal-title":"Sci. China Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Li, X., Zhang, C., Haggerty, A.E., Yan, J., Lan, M., Seu, M., Yang, M., Marlow, M.M., Maldonado-Lasuncion, I., and Cho, B. (2020). The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord. Biomaterials, 245.","DOI":"10.1016\/j.biomaterials.2020.119978"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17207","DOI":"10.1021\/acsami.9b19638","article-title":"Engineering microenvironment for endogenous neural regeneration after spinal cord injury by reassembling extracellular matrix","volume":"12","author":"Liu","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1126\/science.1115462","article-title":"Egfr activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans","volume":"310","author":"Koprivica","year":"2005","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/15476278.2017.1329789","article-title":"The neuronal differentiation microenvironment is essential for spinal cord injury repair","volume":"13","author":"Zhao","year":"2017","journal-title":"Organogenesis"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.actbio.2017.01.009","article-title":"A modified collagen scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair","volume":"51","author":"Fan","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1039\/C8BM00363G","article-title":"Cetuximab and taxol co-modified collagen scaffolds show combination effects for the repair of acute spinal cord injury","volume":"6","author":"Fan","year":"2018","journal-title":"Biomater. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1016\/j.biomaterials.2013.03.062","article-title":"Promotion of neuronal differentiation of neural progenitor cells by using egfr antibody functionalized collagen scaffolds for spinal cord injury repair","volume":"34","author":"Li","year":"2013","journal-title":"Biomaterials"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.biomaterials.2017.05.027","article-title":"Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair","volume":"137","author":"Li","year":"2017","journal-title":"Biomaterials"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Lu, T.M., Houghton, S., Magdeldin, T., Dur\u00e1n, J.G.B., Minotti, A.P., Snead, A., Sproul, A., Nguyen, D.T., Xiang, J., and Fine, H.A. (2021). Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate. Proc Natl Acad Sci USA, 118.","DOI":"10.1073\/pnas.2016950118"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ren, Y., Ao, Y., O\u2019Shea, T.M., Burda, J.E., Bernstein, A.M., Brumm, A.J., Muthusamy, N., Ghashghaei, H.T., Carmichael, S.T., and Cheng, L. (2017). Ependymal cell contribution to scar formation after spinal cord injury is minimal, local and dependent on direct ependymal injury. Sci. Rep., 7.","DOI":"10.1038\/srep41122"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.cell.2018.03.063","article-title":"Single-cell transcriptomics and fate mapping of ependymal cells reveals an absence of neural stem cell function","volume":"173","author":"Shah","year":"2018","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1089\/neu.2014.3575","article-title":"Nestin-positive ependymal cells are increased in the human spinal cord after traumatic central nervous system injury","volume":"32","author":"Cawsey","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10285","DOI":"10.1523\/JNEUROSCI.4915-13.2014","article-title":"Abrogation of beta-catenin signaling in oligodendrocyte precursor cells reduces glial scarring and promotes axon regeneration after cns injury","volume":"34","author":"Rodriguez","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/stem.1959","article-title":"Concise review: Reactive astrocytes and stem cells in spinal cord injury: Good guys or bad guys?","volume":"33","author":"Lukovic","year":"2015","journal-title":"Stem Cells"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s12038-018-9812-z","article-title":"Neuroectodermal stem cells: A remyelinating potential in acute compressed spinal cord injury in rat model","volume":"43","author":"Ramadan","year":"2018","journal-title":"J. Biosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"150","DOI":"10.5607\/en19078","article-title":"Alternatively polarized macrophages regulate the growth and differentiation of ependymal stem cells through the sirt2 pathway","volume":"29","author":"Ma","year":"2020","journal-title":"Exp. Neurobiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6984","DOI":"10.1096\/fj.201903171R","article-title":"Overexpression of rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury","volume":"34","author":"Chen","year":"2020","journal-title":"FASEB J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/cns.13368","article-title":"Immunization with neural-derived peptides increases neurogenesis in rats with chronic spinal cord injury","volume":"26","author":"Garcia","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3171\/2017.12.SPINE17669","article-title":"Methylprednisolone inhibits the proliferation of endogenous neural stem cells in nonhuman primates with spinal cord injury","volume":"29","author":"Ye","year":"2018","journal-title":"J. Neurosurg. Spine"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.4103\/1673-5374.274332","article-title":"Multimodal treatment for spinal cord injury: A sword of neuroregeneration upon neuromodulation","volume":"15","author":"Zheng","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.ultrasmedbio.2018.12.015","article-title":"Ultrasound neuromodulation: A review of results, mechanisms and safety","volume":"45","author":"Blackmore","year":"2019","journal-title":"Ultrasound Med. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Cui, M., Ge, H., Zhao, H., Zou, Y., Chen, Y., and Feng, H. (2017). Electromagnetic fields for the regulation of neural stem cells. Stem Cells Int., 2017.","DOI":"10.1155\/2017\/9898439"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"104","DOI":"10.5115\/acb.2015.48.2.104","article-title":"The effects of repetitive transcranial magnetic stimulation on proliferation and differentiation of neural stem cells","volume":"48","author":"Abbasnia","year":"2015","journal-title":"Anat. Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ceca.2013.11.002","article-title":"Exposure to extremely low-frequency electromagnetic fields inhibits t-type calcium channels via aa\/lte4 signaling pathway","volume":"55","author":"Cui","year":"2014","journal-title":"Cell Calcium"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"He, Y.L., Liu, D.D., Fang, Y.J., Zhan, X.Q., Yao, J.J., and Mei, Y.A. (2013). Exposure to extremely low-frequency electromagnetic fields modulates na+ currents in rat cerebellar granule cells through increase of aa\/pge2 and ep receptor-mediated camp\/pka pathway. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054376"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"E200","DOI":"10.1097\/BRS.0000000000002302","article-title":"Induction of endogenous neural stem cells by extracorporeal shock waves after spinal cord injury","volume":"43","author":"Shin","year":"2018","journal-title":"Spine"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.4103\/1673-5374.330590","article-title":"Neuronal reprogramming in treating spinal cord injury","volume":"17","author":"Chen","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.stem.2021.02.009","article-title":"In vivo reprogramming of ng2 glia enables adult neurogenesis and functional recovery following spinal cord injury","volume":"28","author":"Tai","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Puls, B., Ding, Y., Zhang, F., Pan, M., Lei, Z., Pei, Z., Jiang, M., Bai, Y., Forsyth, C., and Metzger, M. (2020). Regeneration of functional neurons after spinal cord injury via in situ neurod1-mediated astrocyte-to-neuron conversion. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.591883"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.celrep.2016.09.038","article-title":"The p53 pathway controls sox2-mediated reprogramming in the adult mouse spinal cord","volume":"17","author":"Wang","year":"2016","journal-title":"Cell Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.stemcr.2021.05.020","article-title":"Reprogramming astrocytes to motor neurons by activation of endogenous ngn2 and isl1","volume":"16","author":"Zhou","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/path.5151","article-title":"Cells in the adult human spinal cord ependymal region do not proliferate after injury","volume":"246","author":"Norenberg","year":"2018","journal-title":"J. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:45:22Z","timestamp":1760136322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,28]]},"references-count":100,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073728"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073728","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,28]]}}}