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 |
|
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. |
Ficheros | Tamaño | Formato | Ver | Descripción |
---|---|---|---|---|
pubdocument.pdf | 7.694Mb | ![]() | Ver/ | |