Human iPS Cell-derived Cortical Motor Neurons for Functional Recovery after Stroke
Stroke is the leading cause of adult disability, with an estimated 795,000 new strokes per year and almost 1/3 of stroke patients requiring long-term institutional care. Stroke causes disability because of the brain’s limited ability to repair. There are no therapies that promote recovery of function in stroke. Recent studies indicate that stem cell therapies in stroke promote better recovery. These studies are limited by the use of stem cell types that are not specific for the area of brain damage in stroke and the delivery of cells in a generic suspension of fluid. This research project develops a new stem cell therapy for stroke that is specific for the damaged brain region, and uses a delivery system that promotes cell interactions and conforms to the geometry of the damaged area. This project is novel in the stroke field in two ways. First, it uses emerging laboratory techniques to differentiate induced pluripotent stem cells into a brain-region specific cell type. This cell type is more likely to survive and repair in the damaged area and, because it is no longer immature, is less likely to form tumors. Second, this project uses bioengineering to develop a novel sheet of stem/progenitor cells for brain transplantation after stroke. This sheet preserves the cellular interactions that are crucial for stem cell survival and conforms to the geometry of the target brain region, cerebral cortex, to make for a minimally invasive delivery approach.
Stroke is a significant medical problem in California. In the United States, stroke is the leading cause of disability. In California, 1 in 10 Californians have been diagnosed with a stroke and stroke accounts for 1 in 20 hospital discharges. The rate of death after stroke is declining, but the incidence of stroke is increasing. These trends are occurring because better early hospital care prevents stroke deaths, but the aging of the population means that more people are getting strokes. These two trends mean that there will be ever more disabled stroke survivors in California in future years. The studies in this research program develop a new stem cell therapy to promote recovery in stroke. This program goes after an unmet clinical need, as there is no therapy that promotes recovery of function in stroke. This program uses advanced stem cell biology and tissue bioengineering to develop stem cells that are specific for the brain region most commonly damaged in stroke, and a delivery system that is minimally invasive and targets the unique structure of the damaged brain region.