Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

Background: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a...

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Autores: García-Bonilla, María, Ojeda-Pérez, Betsaida, García-Martín, María L., Muñoz-Hernández, M Carmen, Vitorica, Javier, Jiménez, Sebastián, Cifuentes, Manuel, Santos-Ruíz, Leonor, Shumilov, Kirill, Claros, Silvia, Gutiérrez, Antonia, Páez-González, Patricia, Jiménez, Antonio J.
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17985
Acesso em linha:http://hdl.handle.net/20.500.12105/17985
Access Level:acceso abierto
Palavra-chave:Hydrocephalus
Bone marrow-derived mesenchymal stem cells
Spectroscopy
Reactive astrocytes
Hidrocefalia
Células madre mesenquimatosas
Médula osea
Análisis espectral
Animals
Bone Marrow
Bone Marrow Cells
Mice
Mesenchymal Stem Cell Transplantation
Astrocytes
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/17985
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repository_id_str
dc.title.none.fl_str_mv Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
title Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
spellingShingle Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
García-Bonilla, María
Hydrocephalus
Bone marrow-derived mesenchymal stem cells
Spectroscopy
Reactive astrocytes
Hidrocefalia
Células madre mesenquimatosas
Médula osea
Análisis espectral
Animals
Bone Marrow
Bone Marrow Cells
Mice
Hydrocephalus
Mesenchymal Stem Cell Transplantation
Astrocytes
title_short Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
title_full Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
title_fullStr Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
title_full_unstemmed Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
title_sort Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
dc.creator.none.fl_str_mv García-Bonilla, María
Ojeda-Pérez, Betsaida
García-Martín, María L.
Muñoz-Hernández, M Carmen
Vitorica, Javier
Jiménez, Sebastián
Cifuentes, Manuel
Santos-Ruíz, Leonor
Shumilov, Kirill
Claros, Silvia
Gutiérrez, Antonia
Páez-González, Patricia
Jiménez, Antonio J.
author García-Bonilla, María
author_facet García-Bonilla, María
Ojeda-Pérez, Betsaida
García-Martín, María L.
Muñoz-Hernández, M Carmen
Vitorica, Javier
Jiménez, Sebastián
Cifuentes, Manuel
Santos-Ruíz, Leonor
Shumilov, Kirill
Claros, Silvia
Gutiérrez, Antonia
Páez-González, Patricia
Jiménez, Antonio J.
author_role author
author2 Ojeda-Pérez, Betsaida
García-Martín, María L.
Muñoz-Hernández, M Carmen
Vitorica, Javier
Jiménez, Sebastián
Cifuentes, Manuel
Santos-Ruíz, Leonor
Shumilov, Kirill
Claros, Silvia
Gutiérrez, Antonia
Páez-González, Patricia
Jiménez, Antonio J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv [García-Bonilla,M; Ojeda-Pérez,B; Cifuentes,M; Santos-Ruíz,L; Shumilov,K; Claros,S; Gutiérrez,A; Páez-González,P; Jiménez,AJ] Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Malaga, Spain. [García-Bonilla,M; Ojeda-Pérez,B; Cifuentes,M; Santos-Ruíz,L; Shumilov,K; Claros,S; Gutiérrez,A; Páez-González,P; Jiménez,AJ] Instituto de Investigación Biomédica de Málaga (IBIMA), Malaga, Spain. [García-Martín,ML; Muñoz-Hernández,MC] BIONAND, Andalusian Centre for Nanomedicine & Biotechnology (Junta de Andalucía-Universidad de Málaga), Malaga, Spain. [Vitorica,J; Jiménez,S] Department of Molecular Biology and Biochemistry, University of Seville, Seville, Spain. [Vitorica,J; Jiménez,S; Gutiérrez,A] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

dc.subject.none.fl_str_mv Hydrocephalus
Bone marrow-derived mesenchymal stem cells
Spectroscopy
Reactive astrocytes
Hidrocefalia
Células madre mesenquimatosas
Médula osea
Análisis espectral
Animals
Bone Marrow
Bone Marrow Cells
Mice
Hydrocephalus
Mesenchymal Stem Cell Transplantation
Astrocytes
topic Hydrocephalus
Bone marrow-derived mesenchymal stem cells
Spectroscopy
Reactive astrocytes
Hidrocefalia
Células madre mesenquimatosas
Médula osea
Análisis espectral
Animals
Bone Marrow
Bone Marrow Cells
Mice
Hydrocephalus
Mesenchymal Stem Cell Transplantation
Astrocytes
description Background: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. Methods: BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay. Results: Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering. Conclusions: BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01
2020
2020-01-01
2024
2024-02-12
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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 http://hdl.handle.net/20.500.12105/17985
url http://hdl.handle.net/20.500.12105/17985
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central (BMC)
publisher.none.fl_str_mv BioMed Central (BMC)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cellsGarcía-Bonilla, MaríaOjeda-Pérez, BetsaidaGarcía-Martín, María L.Muñoz-Hernández, M CarmenVitorica, JavierJiménez, SebastiánCifuentes, ManuelSantos-Ruíz, LeonorShumilov, KirillClaros, SilviaGutiérrez, AntoniaPáez-González, PatriciaJiménez, Antonio J.HydrocephalusBone marrow-derived mesenchymal stem cellsSpectroscopyReactive astrocytesHidrocefaliaCélulas madre mesenquimatosasMédula oseaAnálisis espectralAnimalsBone MarrowBone Marrow CellsMiceHydrocephalusMesenchymal Stem Cell TransplantationAstrocytesBackground: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. Methods: BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay. Results: Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering. Conclusions: BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.BioMed Central (BMC)[García-Bonilla,M; Ojeda-Pérez,B; Cifuentes,M; Santos-Ruíz,L; Shumilov,K; Claros,S; Gutiérrez,A; Páez-González,P; Jiménez,AJ] Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Malaga, Spain. [García-Bonilla,M; Ojeda-Pérez,B; Cifuentes,M; Santos-Ruíz,L; Shumilov,K; Claros,S; Gutiérrez,A; Páez-González,P; Jiménez,AJ] Instituto de Investigación Biomédica de Málaga (IBIMA), Malaga, Spain. [García-Martín,ML; Muñoz-Hernández,MC] BIONAND, Andalusian Centre for Nanomedicine & Biotechnology (Junta de Andalucía-Universidad de Málaga), Malaga, Spain. [Vitorica,J; Jiménez,S] Department of Molecular Biology and Biochemistry, University of Seville, Seville, Spain. [Vitorica,J; Jiménez,S; Gutiérrez,A] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.20242024-02-1220202020-01-0120202020-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/17985reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/179852026-06-12T12:43:37Z
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