dc.creator | García Bonilla, María | es |
dc.creator | García-Martín, María Luisa | es |
dc.creator | Ojeda Pérez, Betsaida | es |
dc.creator | Muñoz Hernández, Mª Carmen | es |
dc.creator | Vitorica Ferrández, Francisco Javier | es |
dc.creator | Jiménez Muñoz, Sebastián | es |
dc.creator | Cifuentes, Manuel | es |
dc.creator | Santos Ruíz, Leonor | es |
dc.creator | Shumilov, Kirill | es |
dc.creator | Claros, Silvia | es |
dc.creator | Páez González, Patricia | es |
dc.creator | Jiménez, Antonio J. | es |
dc.date.accessioned | 2020-04-03T09:26:15Z | |
dc.date.available | 2020-04-03T09:26:15Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | García Bonilla, M., García-Martín, M.L., Ojeda Pérez, B., Muñoz Hernández, M.C., Vitorica Ferrández, F.J., Jiménez Muñoz, S.,...,Jiménez, .J. (2020). Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells. Stem Cell Research & Therapy, 11 (1, art.121), 1-20. | |
dc.identifier.issn | 1757-6512 | es |
dc.identifier.uri | https://hdl.handle.net/11441/94871 | |
dc.description.abstract | 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. | es |
dc.description.sponsorship | España Instituto Carlos III , PI15/00619 (to AJJ), PI19/00778 (to AJJ and PPG), PI15/00796, and PI18/01557 | es |
dc.description.sponsorship | España Ministerio de Educación, Cultura y Deporte FPU13/02906 | es |
dc.description.sponsorship | España, Ministerio de Economía y Competitividad RYC-2014-16980 | es |
dc.description.sponsorship | España, FEDER Andalucía y Universidad de Málaga UMA18-FEDERJA-277 | es |
dc.format | application/pdf | es |
dc.format.extent | 20 p. | es |
dc.language.iso | eng | es |
dc.publisher | BMC | es |
dc.relation.ispartof | Stem Cell Research & Therapy, 11 (1, art.121), 1-20. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Bone marrow-derived mesenchymal stem cells | es |
dc.subject | Hydrocephalus | es |
dc.subject | Reactive astrocytes | es |
dc.subject | Spectroscopy | es |
dc.title | Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.relation.projectID | PI15/00619 (to AJJ), PI19/00778 (to AJJ and PPG), PI15/00796, and PI18/01557 | es |
dc.relation.projectID | FPU13/02906 | es |
dc.relation.projectID | RYC-2014-16980 | es |
dc.relation.projectID | UMA18-FEDERJA-277 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1186/s13287-020-01626-6 | es |
dc.identifier.doi | 10.1186/s13287-020-01626-6 | es |
dc.journaltitle | Stem Cell Research & Therapy | es |
dc.publication.volumen | 11 | es |
dc.publication.issue | 1, art.121 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 20 | es |
dc.contributor.funder | Instituto de Salud Carlos III | es |
dc.contributor.funder | Ministerio de Educación, Cultura y Deporte (MECD). España | es |
dc.contributor.funder | Ministerio de Economía y Competitividad (MINECO). España | es |
dc.contributor.funder | Plan Operativo FEDER Andalucía | es |
dc.contributor.funder | Universidad de Málaga | es |