Abstract
Stem cell transplantation has been extensively studied as individual therapies for ischemic stroke. The present investigation is an initial effort to combine these methods to achieve increased therapeutic effects after brain ischemia. Cell transplantation may recover massive neuronal loss by replacing damaged brain cells. Undifferentiated mouse embryonic stem (mES) cells were used to induce differentiation in vitro into neuron-like cells with good cell viability for use a graft. In this study, middle cerebral artery occlusion (MCAO) was induced in rats using intra-luminal vascular occlusion, and infused mES cells after MCAO. The animals were examined behaviorally using motor and sensory test with neurological assessment. Motor function of the recipients was gradually improved, whereas little improvement was observed in control rats. This result may suggest that the grafted cells have synaptic connection in the recipient brain. Our study revealed that stem cell transplantation can have a positive effect on behavioral recovery and reduction of infarct size in focal ischemic rats. Consequently after euthanasia, rats were histochemically investigated to explore graft survival with green fluorescent protein (GFP). The mouse embryonic stem cells may have advantage for use as a donor source in various neurological disorders including motor dysfunction.
Highlights
Cell therapy using stem cells is awaited by stroke patients with impaired movement and cognitive functions
We examined the effects of the transplantation of mouse Embryonic stem (ES) cells on behavioral function induced by focal ischemia in rats
Embryonic stem (ES) cells are capable of proliferating and differentiation into neural progenitor cells with the use of induction protocols leading to the development of functionally mature neurons and glial cells[5]
Summary
Cell therapy using stem cells is awaited by stroke patients with impaired movement and cognitive functions. A single injection of mESCs several hours after ischemia onset can reduce infarction size and improve functional outcome in rodent cerebral ischemia models[7] To this end, infusion of growth factors has been shown to promote endogenous progenitor proliferation in response to ischemia and subsequently migrate into the hippocampus to regenerate new neurons[8]. Endogenous neurogenesis and migration of precursor cells may help to replace some lost neurons in brain structures such as striatum[9], transplantation of exogenous stem cells remains to be the most liable way to repair the massive damage in the cerebral cortex after ischemic stroke. There have been many reports that embryonic or neural stem cell graft reduces the infarct size with functional improvement in the experimental models. The priming strategy tested in stem cell transplantation after brain ischemia may represent a clinically feasible manipulation of cell preparation for more effective transplantation therapy
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