Brain tissue recovery in obstructive congenital hydrocephalus after intraventricular transplantation of mesenchymal stem cells

Introduction: Bone marrow-derived mesenchymal stem cells (BM-MSC) are a potential therapeutic tool due to their ability for migrating and producing neuroprotector factors when transplanted. The aim of this study was to evaluate the short-time effects of a BM-MSC experimental therapy in the hyh mouse model with severe obstructive hydrocephalus. Methods: BM-MSC were characterized in vitro and then injected into the ventricles of hyh mice. Wild-type and saline-injected hyh mice were used as controls. Samples were studied by analyzing and comparing mRNA, protein and metabolites level expression in control and damaged tissue. Results: Undifferentiated BM-MSC were found to: i) spread into the periventricular astrocyte reaction region after four days post-injection, and, ii) be producing neuroprotector factors (GDNF and VEGF). Astrocytes located in periventricular edematous region increased their aquaporin-4 expression, as well as Slit2 expression (neuroprotective and anti-inflammatory molecule). There was also a significant reduction of osmolytes such as taurine and neuroexcytotoxic glutamate. Halved apoptotic cell death was detected in the periventricular walls. Conclusions: BM-MSC lead to recovery of the severe neurodegenerative conditions associated to congenital hydrocephalus mediated by reactive astrocytes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech, and PI15/0619 (ISCIII/FEDER)