Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.brainres.2022.148229 http://hdl.handle.net/11449/248162 |
Resumo: | Spinal cord injuries result in severe neurological deficits and neuronal loss, with poor functional recovery. Mesenchymal stem cells have shown promising results; therefore the present objective of this work was to compare motor recovery after treatment with human dental pulp stem cells (hDPSC) cultivated in monolayer (2D) or as spheroids (3D), following avulsion and reimplantation of spinal motor roots in adult rats. Thus, 72 adult female Lewis rats were divided into 4 groups: avulsion (AV); avulsion followed by reimplantation (AR); avulsion associated with reimplant and 2D cell therapy (AR + 2D), and avulsion associated with reimplant and 3D cell therapy (AR + 3D). The application of the cells in 2D and 3D was performed by microsurgery, with subsequent functional assessment using a walking track test (Catwalk system), immunohistochemistry, neuronal survival, and qRT-PCR in 1-, 4-, and 12-weeks post-injury. The animals in the AR + 2D and AR + 3D groups showed the highest neuronal survival rates, and immunofluorescence revealed downregulation of GFAP, and Iba-1, with preservation of synaptophysin, indicating a reduction in glial reactivity, combined with the maintenance of pre-synaptic inputs. There was an increase in anti-inflammatory (IL-4, TGFβ) and a reduction of pro-inflammatory factors (IL-6, TNFα) in animals treated with reimplantation and hDPSC. As for the functional recovery, in all analyzed parameters, the AR + 2D group performed better and was superior to the avulsion alone. Overall, our results indicate that the 2D and 3D cell therapy approaches provide successful immunomodulation and motor recovery, consistent with advanced therapies after spinal cord injury. |
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Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult ratsCell therapyDental pulpSpheroidSpinal cord injurySpinal cord injuries result in severe neurological deficits and neuronal loss, with poor functional recovery. Mesenchymal stem cells have shown promising results; therefore the present objective of this work was to compare motor recovery after treatment with human dental pulp stem cells (hDPSC) cultivated in monolayer (2D) or as spheroids (3D), following avulsion and reimplantation of spinal motor roots in adult rats. Thus, 72 adult female Lewis rats were divided into 4 groups: avulsion (AV); avulsion followed by reimplantation (AR); avulsion associated with reimplant and 2D cell therapy (AR + 2D), and avulsion associated with reimplant and 3D cell therapy (AR + 3D). The application of the cells in 2D and 3D was performed by microsurgery, with subsequent functional assessment using a walking track test (Catwalk system), immunohistochemistry, neuronal survival, and qRT-PCR in 1-, 4-, and 12-weeks post-injury. The animals in the AR + 2D and AR + 3D groups showed the highest neuronal survival rates, and immunofluorescence revealed downregulation of GFAP, and Iba-1, with preservation of synaptophysin, indicating a reduction in glial reactivity, combined with the maintenance of pre-synaptic inputs. There was an increase in anti-inflammatory (IL-4, TGFβ) and a reduction of pro-inflammatory factors (IL-6, TNFα) in animals treated with reimplantation and hDPSC. As for the functional recovery, in all analyzed parameters, the AR + 2D group performed better and was superior to the avulsion alone. Overall, our results indicate that the 2D and 3D cell therapy approaches provide successful immunomodulation and motor recovery, consistent with advanced therapies after spinal cord injury.Universidade Estadual PaulistaLaboratory of Nerve Regeneration Institute of Biology (IB) State University of Campinas (UNICAMP), SPSchool of Chemical Engineering University of Campinas UNICAMP, Av. Albert Einstein, 500Center for the Study of Venoms and Venomous Animals (CEVAP) São Paulo State University (UNESP), SPCenter for the Study of Venoms and Venomous Animals (CEVAP) São Paulo State University (UNESP), SPUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (UNESP)Paes, Sabrina MoreiraCastro, Mateus Vidigal deBarbosa, Rafael MazaPolitti Cartarozzi, LucianaCoser, Lilian de OliveiraKempe, Paula Regina GelinskiDecarli, Monize CaiadoMoraes, Ângela MariaBarraviera, Benedito [UNESP]Ferreira Júnior, Rui Seabra [UNESP]Oliveira, Alexandre Leite Rodrigues de2023-07-29T13:36:11Z2023-07-29T13:36:11Z2023-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.brainres.2022.148229Brain Research, v. 1802.1872-62400006-8993http://hdl.handle.net/11449/24816210.1016/j.brainres.2022.1482292-s2.0-85145996529Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBrain Researchinfo:eu-repo/semantics/openAccess2024-04-11T15:28:26Zoai:repositorio.unesp.br:11449/248162Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:41:37.634617Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats |
title |
Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats |
spellingShingle |
Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats Paes, Sabrina Moreira Cell therapy Dental pulp Spheroid Spinal cord injury |
title_short |
Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats |
title_full |
Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats |
title_fullStr |
Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats |
title_full_unstemmed |
Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats |
title_sort |
Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats |
author |
Paes, Sabrina Moreira |
author_facet |
Paes, Sabrina Moreira Castro, Mateus Vidigal de Barbosa, Rafael Maza Politti Cartarozzi, Luciana Coser, Lilian de Oliveira Kempe, Paula Regina Gelinski Decarli, Monize Caiado Moraes, Ângela Maria Barraviera, Benedito [UNESP] Ferreira Júnior, Rui Seabra [UNESP] Oliveira, Alexandre Leite Rodrigues de |
author_role |
author |
author2 |
Castro, Mateus Vidigal de Barbosa, Rafael Maza Politti Cartarozzi, Luciana Coser, Lilian de Oliveira Kempe, Paula Regina Gelinski Decarli, Monize Caiado Moraes, Ângela Maria Barraviera, Benedito [UNESP] Ferreira Júnior, Rui Seabra [UNESP] Oliveira, Alexandre Leite Rodrigues de |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
Paes, Sabrina Moreira Castro, Mateus Vidigal de Barbosa, Rafael Maza Politti Cartarozzi, Luciana Coser, Lilian de Oliveira Kempe, Paula Regina Gelinski Decarli, Monize Caiado Moraes, Ângela Maria Barraviera, Benedito [UNESP] Ferreira Júnior, Rui Seabra [UNESP] Oliveira, Alexandre Leite Rodrigues de |
dc.subject.por.fl_str_mv |
Cell therapy Dental pulp Spheroid Spinal cord injury |
topic |
Cell therapy Dental pulp Spheroid Spinal cord injury |
description |
Spinal cord injuries result in severe neurological deficits and neuronal loss, with poor functional recovery. Mesenchymal stem cells have shown promising results; therefore the present objective of this work was to compare motor recovery after treatment with human dental pulp stem cells (hDPSC) cultivated in monolayer (2D) or as spheroids (3D), following avulsion and reimplantation of spinal motor roots in adult rats. Thus, 72 adult female Lewis rats were divided into 4 groups: avulsion (AV); avulsion followed by reimplantation (AR); avulsion associated with reimplant and 2D cell therapy (AR + 2D), and avulsion associated with reimplant and 3D cell therapy (AR + 3D). The application of the cells in 2D and 3D was performed by microsurgery, with subsequent functional assessment using a walking track test (Catwalk system), immunohistochemistry, neuronal survival, and qRT-PCR in 1-, 4-, and 12-weeks post-injury. The animals in the AR + 2D and AR + 3D groups showed the highest neuronal survival rates, and immunofluorescence revealed downregulation of GFAP, and Iba-1, with preservation of synaptophysin, indicating a reduction in glial reactivity, combined with the maintenance of pre-synaptic inputs. There was an increase in anti-inflammatory (IL-4, TGFβ) and a reduction of pro-inflammatory factors (IL-6, TNFα) in animals treated with reimplantation and hDPSC. As for the functional recovery, in all analyzed parameters, the AR + 2D group performed better and was superior to the avulsion alone. Overall, our results indicate that the 2D and 3D cell therapy approaches provide successful immunomodulation and motor recovery, consistent with advanced therapies after spinal cord injury. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T13:36:11Z 2023-07-29T13:36:11Z 2023-03-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.brainres.2022.148229 Brain Research, v. 1802. 1872-6240 0006-8993 http://hdl.handle.net/11449/248162 10.1016/j.brainres.2022.148229 2-s2.0-85145996529 |
url |
http://dx.doi.org/10.1016/j.brainres.2022.148229 http://hdl.handle.net/11449/248162 |
identifier_str_mv |
Brain Research, v. 1802. 1872-6240 0006-8993 10.1016/j.brainres.2022.148229 2-s2.0-85145996529 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Brain Research |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129347729489920 |