Therapeutic application of cell transplantation and increased neurogenesis in cerebral infarction]

Cerebral ischemia often results in neuronal loss, leading to the neurological deficits in stroke patients. To obtain the functional recovery after stroke, cell transplantation and enhancement of endogenous neurogenesis may have potential application. Recent evidence has demonstrated that neural stem cells exist in the adult mammalian brain. After cerebral ischemia, newly born neurons were found not only in hippocampal dentate and olfactory bulb but also in hippocampal CA1 and striatum, where neurons were lost after ischemia. Administration of neurotrophic factors or genes encoding them into the lateral venticule could enhance endogenous neurogenesis in experimental ischemia model. Furthermore, we have recently developed non-invasive gene transfer into macrophages infiltrating an infarct to stimulate proliferation of neural stem cells in cerebral infarction. Several strategies including gene therapy and pharmacological approach will be tried in stroke patients in near future. However, it remains unclear whether the number of new-born neurons from endogenous neural stem cells is sufficient for replacement of damaged neurons. Cell transplantation will have the advantage of preparing the large amount of transplanted cells. Human neural stem cells, embryonic stem cells and bone marrow-derived cells will be donor cells in stroke patients. Surprisingly, neuron-like cells derived from human teratoma cell line were already applied in stroke patients. However, ethical aspect will have to be discussed carefully before cells from other individuals are used as donor cells in stroke patients.