Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

• Published in: Stem cell research & therapy 2020-03, Vol.11 (1), p.121-121, Article 121
• Main 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
• Format: Article
• Language: English
• Subjects: Bone marrow; Bone marrow-derived mesenchymal stem cells; Brain; Cell therapy; Comparative analysis; Congenital diseases; Diagnostic imaging; Diseases; Edema; Experiments; Genetic disorders; Glutamate; Hydrocephalus; Intracranial pressure; Mesenchymal stem cells; Metabolites; Neocortex; NMR; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Permeability; Reactive astrocytes; Scanning electron microscopy; Spectroscopy; Spectrum analysis; Stem cell transplantation; Stem cells; Substantia alba; Taurine; Time; Transplants & implants
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-020-01626-6

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. 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 H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance ( H 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. 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. 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.