engleski

Therapeutic potential of neural stem cells in a rat model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive and still incurable neurodegenerative disease characterized by dying of motor neurons, which leads to fatal paralysis and death. Facts that majority of affected individuals are coming from economically active middle-aged population and that they die paralyzed only 3 to 4 years after the first observed symptoms attract attention of the wide biomedical community. The last decade was marked by amazing progress in the field of the neural stem cells (NSC) science. Developed techniques of isolation and differentiation, including obtaining of stem cells from adult tissue opened a wide range of possibilities to test completely new therapeutic approaches in neurodegenerative diseases. Herewith, we report our work with NSC and ALS animal model. In order to get insight in the possible therapeutic application of NSC in a rat model of ALS, specific protocol was developed. It included use of rat experimental model based on superoxide dismutase 1 (SOD1) mutation, characterized by high uniformity of pathological features and high similarity to human disease. NSC from the cortex of 16 days old wild type rat embryos were successfully isolated, neurospheres were cultivated, and high number of undifferentiated and viable cells were obtained. Injection of GFP marked NSC within blood stream of affected animals resulted with presence of the cells within disease affected motor cortex. After 3 days, cells started to differentiate and both neural (Map2 positive) and astrocytic (GFAP positive) markers were recognized. Although approximately 35% of Map2+ cells died by apoptosis, probably caused by cell integration failure within host tissue, remaining Map2+ and majority of GFAP+ cells continue to be present in the motor cortex. Preliminary results showing the presence of synaptic marker synaptotagmin suggest that transplanted cells can survive and integrate within disease affected region. The presence of injected NSC in motor cortex of ALS affected rat brain represent an important step further in cell transplantation therapy of this neurodegenerative disease.

ALS; stem cell therapy

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