Neural stem cell therapy of foetal onset hydrocephalus using the HTx rat as experimental model

AbstractFoetal onset hydrocephalus is a disease starting early in embryonic life; in many cases it results from a cell junction pathology of neural stem (NSC) and neural progenitor (NPC) cells forming the ventricular zone (VZ) and sub-ventricular zone (SVZ) of the developing brain. This pathology results in disassembling of VZ and loss of NSC/NPC, a phenomenon known as VZ disruption. At the cerebral aqueduct, VZ disruption triggers hydrocephalus while in the telencephalon, it results in abnormal neurogenesis. This may explain why derivative surgery does not cure hydrocephalus. NSC grafting appears as a therapeutic opportunity. The present investigation was designed to find out whether this is a likely possibility. HTx rats develop hereditary hydrocephalus; 30 –40% of newborns are hydrocephalic (hyHTx) while their littermates are not (nHTx). NSC/NPC from the VZ/SVZ of nHTx rats were cultured into neurospheres that were then grafted into a lateral ventricle of 1-, 2- or 7-day-old hyHTx. Once in the cerebrospinal fluid, neurospheres disassembled and the f reed NSC homed at the areas of VZ disruption. A population of homed cells generated new multiciliated ependyma at the sites where the ependyma was missing due to the inherited pathology. Another population of NSC homed at the disrupted VZ differentiated into βIII-tubulin+ spherical cells likely cor responding to neuroblasts that progressed into the parenchyma. The final fate of these cells could not be established due to the...
Source: Cell and Tissue Research - Category: Cytology Source Type: research