Grant: Project Grant

Ischemic stroke results in loss of both neurons and blood vessels. Stem cell based therapy is a promising strategy for the treatment of stroke by providing robust exogenous cells for tissue regeneration. we propose to develop an optimal transplantation approach by targeting regeneration of both neurons and blood vessels, which can be further potentiated through preconditioning strategy.The beneficial reciprocal interaction between transplanted neural stem cells and blood vessel stem cells will synergistically not only restore cerebral blood flow and but also enhance the generation of enormous quantitates of mature neurons to support stroke functional recovery. Finally, the combination of enriched rehabilitation with the cell therapy will provide a clinically relevant treatment model that has potential to enhance functional integration of exogenous cells into brain and improve behavioral recovery. We will perform stroke surgery in different cohorts of rats who will receive cell transplantation surgery 1 week after stroke with either human neural stem cells or human blood vessel stem cells alone, or in combination. In a separate set of experiments, we will combine enriched rehabilitation with co-transplantation cell surgery in the groups of rats who will receive stroke surgery 1 week before. To measure outcomes of these combination therapies, we will evaluate brain damage, quantify the number of grafted cells in the damaged brain, assess functional integration of exogenous neurons and blood vessels in the brain, and assess behavioural recovery profiles. Optimizing the cell-based therapies through a novel preconditioning approach, co-transplantation of both neural and blood vessel stem cells in combining with enriched rehabilitation provides a clinically relevant treatment model that has potential to enhance functional integration of robust exogenous grafted cells into undamaged brain regions and improve behavioral recovery following stroke.