Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesen-chymal stem cells (MSC...

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Autores: Bonilla, Pablo, Hernández Martín, Joaquim|||0000-0003-1409-5568, Giraldo, Esther, González-Pérez, Miguel A., Alastrue-Agudo, Ana|||0000-0002-9326-2119, Elkhenany, Hoda|||0000-0003-2638-8640, Vicent, María J., Navarro, X. (Xavier)|||0000-0001-9849-902X, Edel, Michael J.|||0000-0002-5619-8680, Moreno-Manzano, Victoria|||0000-0002-6035-9491
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:250784
Acesso em linha:https://ddd.uab.cat/record/250784
https://dx.doi.org/urn:doi:10.3390/ijms22115966
Access Level:acceso abierto
Palavra-chave:Spinal cord injury
Stem cells
Curcumin
Neuroprotection
Polymer-drug conjugate
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spelling Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatmentBonilla, PabloHernández Martín, Joaquim|||0000-0003-1409-5568Giraldo, EstherGonzález-Pérez, Miguel A.Alastrue-Agudo, Ana|||0000-0002-9326-2119Elkhenany, Hoda|||0000-0003-2638-8640Vicent, María J.Navarro, X. (Xavier)|||0000-0001-9849-902XEdel, Michael J.|||0000-0002-5619-8680Moreno-Manzano, Victoria|||0000-0002-6035-9491Spinal cord injuryStem cellsCurcuminNeuroprotectionPolymer-drug conjugateWe currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesen-chymal stem cells (MSC), and a pH-responsive polyacetal-curcumin nanoconjugate (PA-C) that al-lows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment pro-tected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccha-ride-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/250784https://dx.doi.org/urn:doi:10.3390/ijms22115966reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-095872-B-C21open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2507842026-06-06T12:50:31Z
dc.title.none.fl_str_mv Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
title Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
spellingShingle Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
Bonilla, Pablo
Spinal cord injury
Stem cells
Curcumin
Neuroprotection
Polymer-drug conjugate
title_short Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
title_full Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
title_fullStr Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
title_full_unstemmed Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
title_sort Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
dc.creator.none.fl_str_mv Bonilla, Pablo
Hernández Martín, Joaquim|||0000-0003-1409-5568
Giraldo, Esther
González-Pérez, Miguel A.
Alastrue-Agudo, Ana|||0000-0002-9326-2119
Elkhenany, Hoda|||0000-0003-2638-8640
Vicent, María J.
Navarro, X. (Xavier)|||0000-0001-9849-902X
Edel, Michael J.|||0000-0002-5619-8680
Moreno-Manzano, Victoria|||0000-0002-6035-9491
author Bonilla, Pablo
author_facet Bonilla, Pablo
Hernández Martín, Joaquim|||0000-0003-1409-5568
Giraldo, Esther
González-Pérez, Miguel A.
Alastrue-Agudo, Ana|||0000-0002-9326-2119
Elkhenany, Hoda|||0000-0003-2638-8640
Vicent, María J.
Navarro, X. (Xavier)|||0000-0001-9849-902X
Edel, Michael J.|||0000-0002-5619-8680
Moreno-Manzano, Victoria|||0000-0002-6035-9491
author_role author
author2 Hernández Martín, Joaquim|||0000-0003-1409-5568
Giraldo, Esther
González-Pérez, Miguel A.
Alastrue-Agudo, Ana|||0000-0002-9326-2119
Elkhenany, Hoda|||0000-0003-2638-8640
Vicent, María J.
Navarro, X. (Xavier)|||0000-0001-9849-902X
Edel, Michael J.|||0000-0002-5619-8680
Moreno-Manzano, Victoria|||0000-0002-6035-9491
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Spinal cord injury
Stem cells
Curcumin
Neuroprotection
Polymer-drug conjugate
topic Spinal cord injury
Stem cells
Curcumin
Neuroprotection
Polymer-drug conjugate
description We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesen-chymal stem cells (MSC), and a pH-responsive polyacetal-curcumin nanoconjugate (PA-C) that al-lows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment pro-tected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccha-ride-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv 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://ddd.uab.cat/record/250784
https://dx.doi.org/urn:doi:10.3390/ijms22115966
url https://ddd.uab.cat/record/250784
https://dx.doi.org/urn:doi:10.3390/ijms22115966
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 https://doi.org/10.13039/501100011033 RTI2018-095872-B-C21
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://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
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eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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