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Title: Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
Authors: 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.
metadata.dc.contributor.authoraffiliation: [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.
Keywords: Hydrocephalus;Bone marrow-derived mesenchymal stem cells;Spectroscopy;Reactive astrocytes;Hidrocefalia;Células madre mesenquimatosas;Médula osea;Análisis espectral
metadata.dc.subject.mesh: Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Bone Marrow
Medical Subject Headings::Anatomy::Cells::Bone Marrow Cells
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Hydrocephalus
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Mesenchymal Stem Cell Transplantation
Medical Subject Headings::Anatomy::Cells::Neuroglia::Astrocytes
Issue Date: 2020
Publisher: BioMed Central, Springer Nature
Citation: García-Bonilla M, Ojeda-Pérez B, García-Martín ML, Muñoz-Hernández MC, Vitorica J, Jiménez S, et al. Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells. Stem Cell Res Ther. 2020 Mar 17;11(1):121
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.
metadata.dc.identifier.doi: 10.1186/s13287-020-01626-6
ISSN: 1757-6512 (Online)
Appears in Collections:01- Artículos - BIONAND - Centro Andaluz de Nanomedicina y Biotecnología
01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga

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