engleski

Distribution, differentiation and survival of intravenously administered neural stem cells in a rat model of amyotrophic lateral sclerosis

The transplantation of neural stem cells (NSCs) is a challenging therapeutic strategy for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). To provide insight into the potential of the intravenous delivery of NSCs, we evaluated the delivery of NSCs marked with green fluorescent protein to the central nervous system (CNS) via intravenous tail vein injections in an ALS model. The injected cell fates were followed one, three and seven days after transplantation. The highest efficiency of cell delivery to the CNS was found in symptomatic ALS (up to 13%), moderate in presymptomatic ALS (up to 6%) and the lowest in wild type animals (up to 0.3%). NSCs injected into ALS animals preferentially colonised the motor cortex, hippocampus, and spinal cord, and their differentiation was characterised by a decrease of nestin expression and the appearance of MAP2, GFAP, O4 and CD68 positive cells. Tumor necrosis factor (TNF) administration increased the CNS delivery of transplanted cells in wild type and presymptomatic, but not ALS symptomatic animals. Moreover, a TNF-related increase in NSC differentiation and survival was detected. Apoptosis was detected as the main cause of the loss of transplanted cells and it was influenced by TNF. Although three days after TNF treatment cell death was accelerated, TNF slowed down apoptosis after seven days. This study provides elementary facts about the process occurring after NSCs leave the blood stream and enter the nervous tissue affected by inflammation/degeneration, which should help facilitate the planning of future bench-to-bedside translational projects.

stem cells; amyotrophic lateral sclerosis; rat

nije evidentirano