engleski

Neural stem cells in a rat model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive and terminal neurodegenerative disease specifically affecting motoneurons. Death caused by paralysis occurs only 3 to 4 years after the first observed symptom. Although genetic background of 90% of the cases is not defined, uniformity of pathological features in familial superoxide dismutase 1 (SOD1) mutation yielded high interest for this mutation and corresponding animal model. In order to get insight in the cellular mechanisms involved in pathogenesis of amyotrophic lateral sclerosis, in vitro differentiation of neural stem cells obtained from embryo cortex of SOD1 mutant rat were compared to the wild type control. Moreover, their therapeutic potential using blood delivery was tested. In vitro differentiation of SOD1 cells revealed differences in comparison to their wild type counterparts. While in wild type cell cultures presence of nestin marked early phase in the neural stem cells development, 100% of cells in SOD1 cultures with advanced neuron - like morphology were simultaneously expressing nestin and neuron specific MAP2. Moreover, major differences in cell clustering patterns were observed. In order to test whether in vitro cultured cells can be delivered through circulation to the brain of symptomatic SOD1 mutant rat, 10 millions of wild type nestin/GFP positive cells were injected in the rat tail vein. After 3 days, cells were found in the cortex and hippocampus of treated animals. As pathological process in amyotrophic lateral sclerosis affects scattered regions of the brain and the spinal cord, adapted therapeutic blood delivery based approach was applied. We believe that presence of injected neural stem cells in different regions of ALS affected rat brain represents important step further in cell transplantation therapy of this neurodegenerative disease.

ALS; neural stem cell therapy

nije evidentirano