Cell-based therapies and functional recovery in experimental stroke rats

Stroke is the third leading cause of deaths in Western countries, and more importantly, it is a leading cause of adult disability. Restorative approaches such as cell-based therapies are clinically appealing as it might be possible to help stroke patients even when treatment is initiated days or weeks after the ischemic insult. Noninvasive intra-vascular administration of cells, which provides a broad distribution of cells to the close proximity of ischemic tissue, has perhaps the most immediate access to clinical applications. For example, intravenous infusion of human umbilical cord blood (HUCB) cells and bone marrow stromal (BMS) cells has been shown to improve sensorimotor functions in rats subjected to focal cerebral ischemia. Interestingly, entry of cells into the central nervous system is not needed for the beneficial effect indicating that peripheral mechanisms or trophic factors may play a role. Another approach is a stereotaxic transplantation of cells into the brain. Our recent data suggest, that subventricular zone (SVZ)-derived mouse neural stem cells or human embryonic stem cell (hESC)-derived neural precursors, when transplanted close to the infarct, do provide some improvement in sensorimotor function after focal cerebral ischemia in rats, but do not restore more complicated sensorimotor function such as skilled reaching. The major problem seems to be a marginal long-term survival rate of transplanted cells. Thus, more work is needed to define the optimal cell type, route of administration, and timing of administration after cerebral ischemia to support cell survival. This would also ensure safe and effective translation of experimental results into clinical practice.