{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T23:21:23Z","timestamp":1778973683935,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3 Marat\u00f3 TV3","award":["2017\/refs.20172230"],"award-info":[{"award-number":["2017\/refs.20172230"]}]},{"name":"Fundaci\u00f3 Marat\u00f3 TV3","award":["20172231"],"award-info":[{"award-number":["20172231"]}]},{"name":"Fundaci\u00f3 Marat\u00f3 TV3","award":["RTI2018-095872-B-C21"],"award-info":[{"award-number":["RTI2018-095872-B-C21"]}]},{"name":"Fundaci\u00f3 Marat\u00f3 TV3","award":["PDI2021-1243590B-I00\/ERDF"],"award-info":[{"award-number":["PDI2021-1243590B-I00\/ERDF"]}]},{"name":"Agencia Valenciana de Innovaci\u00f3n (AVI)","award":["2017\/refs.20172230"],"award-info":[{"award-number":["2017\/refs.20172230"]}]},{"name":"Agencia Valenciana de Innovaci\u00f3n (AVI)","award":["20172231"],"award-info":[{"award-number":["20172231"]}]},{"name":"Agencia Valenciana de Innovaci\u00f3n (AVI)","award":["RTI2018-095872-B-C21"],"award-info":[{"award-number":["RTI2018-095872-B-C21"]}]},{"name":"Agencia Valenciana de Innovaci\u00f3n (AVI)","award":["PDI2021-1243590B-I00\/ERDF"],"award-info":[{"award-number":["PDI2021-1243590B-I00\/ERDF"]}]},{"name":"MCIN\/AEI\/\/10.13039\/501100011033","award":["2017\/refs.20172230"],"award-info":[{"award-number":["2017\/refs.20172230"]}]},{"name":"MCIN\/AEI\/\/10.13039\/501100011033","award":["20172231"],"award-info":[{"award-number":["20172231"]}]},{"name":"MCIN\/AEI\/\/10.13039\/501100011033","award":["RTI2018-095872-B-C21"],"award-info":[{"award-number":["RTI2018-095872-B-C21"]}]},{"name":"MCIN\/AEI\/\/10.13039\/501100011033","award":["PDI2021-1243590B-I00\/ERDF"],"award-info":[{"award-number":["PDI2021-1243590B-I00\/ERDF"]}]},{"name":"Project 964562 (RISEUP)","award":["2017\/refs.20172230"],"award-info":[{"award-number":["2017\/refs.20172230"]}]},{"name":"Project 964562 (RISEUP)","award":["20172231"],"award-info":[{"award-number":["20172231"]}]},{"name":"Project 964562 (RISEUP)","award":["RTI2018-095872-B-C21"],"award-info":[{"award-number":["RTI2018-095872-B-C21"]}]},{"name":"Project 964562 (RISEUP)","award":["PDI2021-1243590B-I00\/ERDF"],"award-info":[{"award-number":["PDI2021-1243590B-I00\/ERDF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neural precursor cell (NPC) transplantation represents a promising therapy for treating spinal cord injuries (SCIs); however, despite successful results obtained in preclinical models, the clinical translation of this approach remains challenging due, in part, to the lack of consensus on an optimal cell source for human neuronal cells. Depending on the cell source, additional limitations to NPC-based therapies include high tumorigenic potential, alongside poor graft survival and engraftment into host spinal tissue. We previously demonstrated that NPCs derived from rat fetal spinal cords primed with a polyglutamate (PGA)-conjugated form of the Rho\/Rock inhibitor fasudil (PGA-SS-FAS) displayed enhanced neuronal differentiation and graft survival when compared to non-primed NPCs. We now conducted a similar study of human-fetal-spinal-cord-derived NPCs (hfNPCs) from legal gestational interruptions at the late gestational stage, at 19\u201321.6 weeks. In vitro, expanded hfNPCs retained neural features, multipotency, and self-renewal, which supported the development of a cell banking strategy. Before transplantation, we established a simple procedure to prime hfNPCs by overnight incubation with PGA-SS-FAS (at 50 \u03bcM FAS equiv.), which improved neuronal differentiation and overcame neurite-like retraction after lysophosphatidic-acid-induced Rho\/Rock activation. The transplantation of primed hfNPCs into immune-deficient mice (NU(NCr)-Foxn1nu) immediately after the eighth thoracic segment compression prompted enhanced migration of grafted cells from the dorsal to the ventral spinal cord, increased preservation of GABAergic inhibitory Lbx1-expressing and glutamatergic excitatory Tlx3-expressing somatosensory interneurons, and elevated the numbers of preserved, c-Fos-expressing, activated neurons surrounding the injury epicenter, all in a low percentage. Overall, the priming procedure using PGA-SS-FAS could represent an alternative methodology to improve the capabilities of the hfNPC lines for a translational approach for acute SCI treatment.<\/jats:p>","DOI":"10.3390\/cells11203304","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T20:35:55Z","timestamp":1666298155000},"page":"3304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transplantation of Human-Fetal-Spinal-Cord-Derived NPCs Primed with a Polyglutamate-Conjugated Rho\/Rock Inhibitor in Acute Spinal Cord Injury"],"prefix":"10.3390","volume":"11","author":[{"given":"Esther","family":"Giraldo","sequence":"first","affiliation":[{"name":"Neuronal and Tissue Regeneration Laboratory, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012 Valencia, Spain"},{"name":"Department of Biotechnology. Universitat Polit\u00e8cnica de Val\u00e8ncia, E-46022 Valencia, Spain"},{"name":"UPV-CIPF Joint Research Unit Disease Mechanisms and Nanomedicine, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Neuronal and Tissue Regeneration Laboratory, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-8383","authenticated-orcid":false,"given":"Mara","family":"Mellado","sequence":"additional","affiliation":[{"name":"Neuronal and Tissue Regeneration Laboratory, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2415-1626","authenticated-orcid":false,"given":"Pablo","family":"Garcia-Manau","sequence":"additional","affiliation":[{"name":"Maternal-Foetal Medicine Unit, Vall d\u2019Hebron Hospital Campus, E-08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8801-5677","authenticated-orcid":false,"given":"Carlota","family":"Rodo","sequence":"additional","affiliation":[{"name":"Maternal-Foetal Medicine Unit, Vall d\u2019Hebron Hospital Campus, E-08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9326-2119","authenticated-orcid":false,"given":"Ana","family":"Alastrue","sequence":"additional","affiliation":[{"name":"Neuronal and Tissue Regeneration Laboratory, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Lopez","sequence":"additional","affiliation":[{"name":"Neuronal and Tissue Regeneration Laboratory, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena Carreras","family":"Moratonas","sequence":"additional","affiliation":[{"name":"Maternal-Foetal Medicine Unit, Vall d\u2019Hebron Hospital Campus, E-08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0644-7757","authenticated-orcid":false,"given":"Ferran","family":"Pellise","sequence":"additional","affiliation":[{"name":"Spine Surgery Unit, Hospital Universitari Vall d\u2019Hebron, E-08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-7486","authenticated-orcid":false,"given":"Sne\u017eana","family":"\u0110or\u0111evi\u0107","sequence":"additional","affiliation":[{"name":"Polymer Therapeutics Laboratory, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7771-3373","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Vicent","sequence":"additional","affiliation":[{"name":"Polymer Therapeutics Laboratory, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-9491","authenticated-orcid":false,"given":"Victoria","family":"Moreno Manzano","sequence":"additional","affiliation":[{"name":"Neuronal and Tissue Regeneration Laboratory, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe, E-46012 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dalamagkas, K., Tsintou, M., Seifalian, A., and Seifalian, A.M. 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