Grant Award Details
iPS-Interneuron Transplantation for Neural Repair after Stroke
<p style="">Stroke is the leading cause of adult disability. Because of the aging population and increasing risk factors, such as diabetes, the prevalence of stroke is increasing in the US: currently there are more people living with stroke than with Alzheimer’s and Parkinson’s diseases combined. There is no therapy that promotes tissue repair and recovery in stroke. A major limitation to a neural repair therapy in stroke is that the circuitry of the brain is complex and poorly understood, and it is difficult to design a drug or cell therapy that can reconstitute this circuitry. The studies in this grant hypothesized that a stem cell therapy based on a cell type that normally migrates widely in the brain and integrates into brain circuits in development would be capable of doing the same after stroke, and repairing damaged brain circuits. This cell type is the interneuron, and is developed by differentiating human induced pluripotent stem cells (hiPS cells) using a combination of small molecules (3 protein inhibitors, or “3i”). The cell line is termed hiPS-3i cells. Transplantation of hiPS-3i cells into the stroke cavity produces behavioral recovery when done at two clinically relevant time points: a subacute time point after stroke (the first week) and a chronic time point after stroke, equivalent to months after stroke in human patients. The transplantation of hiPS-3i cells reduces tissue damage that occurs progressively over time after stroke, and reduces scarring and inflammation. These results identify a neural repair therapy for stroke, which can be delivered at times when stroke patients are out of the hospital from their acute stroke event, and which is effective at early and late time points in this disease.</p>
Grant Application Details
- iPS-Interneuron Transplantation for Neural Repair after Stroke
To determine if transplantation of iPS-interneurons cells (iPS-3i cells) enhances functional recovery in stroke.
Successful completion of the proposed studies will develop a brain repair therapy for stroke, an unmet clinical need with significant impact on society.
Major Proposed Activities
- To determine the recovery effect of transplantation of iPS-3i cells in the mouse at subacute (7 days after stroke) and chronic (21 days) points, using measures that mimic human functional recovery.
- To determine the integration and circuit properties of transplanted iPS-3i cells in stroke at subacute and chronic time points using anatomical and optogenetic circuit mapping.
Statement of Benefit to California:
Stroke is the leading cause of adult disability. There is no medical therapy that promotes recovery in this disease. This research will test the effect of a new cellular transplant strategy to promote recovery in stroke, using induced pluripotent stem cells that have been differentiated into interneurons. These cells have markedly improved survival, migration and engraftment than previous stem cell approaches in stroke, and induce a form of plasticity that mimics the limited recovery in stroke.
Source URL: https://www.cirm.ca.gov/our-progress/awards/ips-interneuron-transplantation-neural-repair-after-stroke