Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury

[EN] 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 opt...

Descripción completa

Detalles Bibliográficos
Autores: Giraldo, Esther|||0000-0001-5488-3011, Bonilla, Pablo, Mellado, Mara, García-Manau, Pablo, Rodó, Carlota, Alastrue, Ana, López, Eric, Carreras Moratonas, Elena, Pellisé, Ferran, Dordevic, Snezana, Vicent, María J., Moreno Manzano, Victoria
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/214060
Acceso en línea:https://riunet.upv.es/handle/10251/214060
Access Level:acceso abierto
Palabra clave:NPC transplantation
Rho/ROCK kinase inhibition
Cell priming
Human fetal neural precursor
Spinal cord injury
BIOLOGIA CELULAR
id ES_dbffa22f3a260be5cfa4215a4050ca21
oai_identifier_str oai:riunet.upv.es:10251/214060
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury
title Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury
spellingShingle Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury
Giraldo, Esther|||0000-0001-5488-3011
NPC transplantation
Rho/ROCK kinase inhibition
Cell priming
Human fetal neural precursor
Spinal cord injury
BIOLOGIA CELULAR
title_short Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury
title_full Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury
title_fullStr Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury
title_full_unstemmed Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury
title_sort Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord Injury
dc.creator.none.fl_str_mv Giraldo, Esther|||0000-0001-5488-3011
Bonilla, Pablo
Mellado, Mara
García-Manau, Pablo
Rodó, Carlota
Alastrue, Ana
López, Eric
Carreras Moratonas, Elena
Pellisé, Ferran
Dordevic, Snezana
Vicent, María J.
Moreno Manzano, Victoria
author Giraldo, Esther|||0000-0001-5488-3011
author_facet Giraldo, Esther|||0000-0001-5488-3011
Bonilla, Pablo
Mellado, Mara
García-Manau, Pablo
Rodó, Carlota
Alastrue, Ana
López, Eric
Carreras Moratonas, Elena
Pellisé, Ferran
Dordevic, Snezana
Vicent, María J.
Moreno Manzano, Victoria
author_role author
author2 Bonilla, Pablo
Mellado, Mara
García-Manau, Pablo
Rodó, Carlota
Alastrue, Ana
López, Eric
Carreras Moratonas, Elena
Pellisé, Ferran
Dordevic, Snezana
Vicent, María J.
Moreno Manzano, Victoria
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biotecnología
Centro Avanzado de Microbiología Aplicada
Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural
European Commission
Fundació La Marató de TV3
Agencia Estatal de Investigación
European Regional Development Fund
Ministerio de Ciencia e Innovación
Agència Valenciana de la Innovació
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv NPC transplantation
Rho/ROCK kinase inhibition
Cell priming
Human fetal neural precursor
Spinal cord injury
BIOLOGIA CELULAR
topic NPC transplantation
Rho/ROCK kinase inhibition
Cell priming
Human fetal neural precursor
Spinal cord injury
BIOLOGIA CELULAR
description [EN] 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 19-21.6 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 ¿M 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-10-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://riunet.upv.es/handle/10251/214060
url https://riunet.upv.es/handle/10251/214060
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 RTI2018-095872-B-C21 NUEVO BIOMATERIAL BIO-ACTIVO PARA LA REGENERACION DE LESIONES MEDULARES
European Commission https://doi.org/10.13039/501100000780 H2020 964562 Regeneration of Injured Spinal cord by Electro pUlsed bio-hybrid imPlant
Fundació La Marató de TV3 Fundació La Marató de TV3 20172230
Fundació La Marató de TV3 Fundació La Marató de TV3 20172231
Agència Valenciana de la Innovació https://doi.org/10.13039/501100016028 INNVAL10%2F19%2F047
Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 PID2021-1243590B-I00
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento (by)
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento (by)
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname:Universitat Politècnica de València (UPV)
instname_str Universitat Politècnica de València (UPV)
reponame_str RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
collection RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421727860129792
spelling Transplantation of Human Fetal Spinal cord-derived NPCs Primed with a Polyglutamate-conjugated Rho/Rock Inhibitor as a Therapy for Acute Spinal Cord InjuryGiraldo, Esther|||0000-0001-5488-3011Bonilla, PabloMellado, MaraGarcía-Manau, PabloRodó, CarlotaAlastrue, AnaLópez, EricCarreras Moratonas, ElenaPellisé, FerranDordevic, SnezanaVicent, María J.Moreno Manzano, VictoriaNPC transplantationRho/ROCK kinase inhibitionCell primingHuman fetal neural precursorSpinal cord injuryBIOLOGIA CELULAR[EN] 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 19-21.6 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 ¿M 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.This research was funded by Fundacio Marato TV3 2017/refs.20172230, 20172231, Agencia Valenciana de Innovacion (AVI) (INNVAL10/19/047 and Grants RTI2018-095872-B-C21 and PDI20211243590B-I00/ERDF funded by MCIN/AEI//10.13039/501100011033 and by ERDF A way of making Europe). This project was also funded by Project 964562 (RISEUP), H2020 FetOpen program.MDPIDepartamento de BiotecnologíaCentro Avanzado de Microbiología AplicadaEscuela Técnica Superior de Ingeniería Agronómica y del Medio NaturalEuropean CommissionFundació La Marató de TV3Agencia Estatal de InvestigaciónEuropean Regional Development FundMinisterio de Ciencia e InnovaciónAgència Valenciana de la InnovacióRepositorio Institucional de la Universitat Politècnica de València Riunet20222022-10-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/214060reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 RTI2018-095872-B-C21 NUEVO BIOMATERIAL BIO-ACTIVO PARA LA REGENERACION DE LESIONES MEDULARESEuropean Commission https://doi.org/10.13039/501100000780 H2020 964562 Regeneration of Injured Spinal cord by Electro pUlsed bio-hybrid imPlantFundació La Marató de TV3 Fundació La Marató de TV3 20172230Fundació La Marató de TV3 Fundació La Marató de TV3 20172231Agència Valenciana de la Innovació https://doi.org/10.13039/501100016028 INNVAL10%2F19%2F047Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 PID2021-1243590B-I00open accesshttp://purl.org/coar/access_right/c_abf2Reconocimiento (by)http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riunet.upv.es:10251/2140602026-06-13T07:49:27Z
score 15.811543

Similares en LA Referencia