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...
| Autores: | , , , , , , , , , , , , |
|---|---|
| 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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España |
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| 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 |
|
| _version_ |
1869415350901145600 |
| 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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15,812429 |