Artículo
Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
Autor/es | García Bonilla, María
García-Martín, María Luisa Ojeda Pérez, Betsaida Muñoz Hernández, Mª Carmen Vitorica Ferrández, Francisco Javier Jiménez Muñoz, Sebastián Cifuentes, Manuel Santos Ruíz, Leonor Shumilov, Kirill Claros, Silvia Páez González, Patricia Jiménez, Antonio J. |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2020 |
Fecha de depósito | 2020-04-03 |
Publicado en |
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Resumen | 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, ... 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. |
Agencias financiadoras | Instituto de Salud Carlos III Ministerio de Educación, Cultura y Deporte (MECD). España Ministerio de Economía y Competitividad (MINECO). España Plan Operativo FEDER Andalucía Universidad de Málaga |
Identificador del proyecto | PI15/00619 (to AJJ), PI19/00778 (to AJJ and PPG), PI15/00796, and PI18/01557
FPU13/02906 RYC-2014-16980 UMA18-FEDERJA-277 |
Cita | 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. |
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