Pemanfaatan bone marrow mesenchymal stem cell untuk terapi model epilepsi

Abstract

Epilepsy is a chronic neurologic disease, caused by abnormal electrical activity in the brain. Uncontrolled medication using the currently available antiepileptic drugs may result in low quality of life. Bone marrow mesenchymal stem cell (bMSCs), one source of stem cell that is multipotent, can be given as an alternative treatment for intractable epilepsy. This research was aimed to (1) analyze the effect of chemical substance that can damaged the brain, to make a suitable animal model for epilepsy, (2) study of the culture bMSCs, and induced to become neurons in vitro neuron progenitor cells, before it can be transplanted to the animal model, (3) observe the effect of different dosages of bMSCs, and comparing the 2 routes of administration, through an intravenous line or a direct intracerebral approach. This study used 46 Spraque Dawley rats, aged 2 months which were divided to 7 groups consisted 6 rats each (1) negative control group, were given only 1ml NaCl 0.9% intravenous, (2) development of animal group model, 3 rats were given lidocaine 90mg/kg, 3 rats injected with bicuculine 8mg/kg, 1 rat was sacrificed each at the point of 24 hours, 3 days and 7 days after treatment, (3) positive epilepsy group, injected with bicuculine 8mg/kg intraperitoneally, and 3 rats were sacrificed each after 3 weeks and 6 weeks, (4-7) epilepsy group, after injected with bicuculine 8mg/kg intraperitoneally, at day-7 received bMSCs injection, each using 3x2x105 cell intravenous, 1x5x106 cell intravenous, neuron progenitor at 1x2x106 cell intravenous and neuron progenitor at 1x2x105 cell intracerebral. The result of this study showed that bicuculine injection, as a GABA-antagonist, was better when applied to create an epilepsy animal model. The most severe irreversible damaged occurred after the 7th day of treatment. The amount of cells of bMSCs culture at the 4th and 5th passages was sufficient to be transplanted, and the induction of neuron progenitor with basic fibroblast growth factor and epidermal growth factor was seen by noticing the change of the fibroblasts to neurons. The activity of bMSCs to regenerated neurons could be seen that injection of bMSCs 3x2x105 results the highest number of survived neurons. There was no systemic effect of bMSCs. From this study concluded that bMSCs improved regenerate the damage of hippocampal area caused by seizure in epilepsy model animals. A low dose, intravenous administration, given repeatedly every 2 weeks gives a better respon compared to a bolus with high dose intravenous and , intracerebrally. bMSCs treatment was better than progenitor neuron treatment.