This project tested the feasibility of using human embryonic stem cell (hESC)-derived neural stem/progenitor cells (hNPCs) expressing constitutively active MEF2C (MEF2CA) transcription factor as a cell therapy candidate for stroke. A rodent stroke model (spontaneously hypertensive rat (SHR) model of focal stroke) was used for testing behavioral and histological improvement after transplantation with hNPCs stably expressing MEF2CA (designated here as stable-MEF2CA hNPCs). We first compared two different types of MEF2CA-programmed candidate stem cell products under two expression systems (stable transformant vs. transient AAV-infection) and found that the stable-MEF2CA hNPC line was superior. In order to determine the optimal therapeutic dose of cells for transplantation, we next conducted dose-response experiments by transplanting three doses (500K, 1 million, or 3 million cells per animal) of stable-MEF2CA-hNPCs into the brain of our rat model after stroke. We found that the dose of 3 million cells exhibited limiting toxicity. In contrast, the animals that received either the 1 million or 500K dose of cells showed significant behavioral improvements over a 12-week observation period, along with histological evidence of graft survival and differentiation into neurons in the absence of noticeable inflammation, overt toxicity, tumor formation/hyperproliferation, or presence of grafted cells in ectopic locations in the body. Since we did not observe any clear advantage using a higher dose (1 million cells/animal), we conclude that a dose of 500K cells in rodents is most effective, and an equivalent dose estimated based on this rodent dose will serve as a starting point for future testing of this therapeutic candidate. In summary, we have achieved each of the success criteria that had been set for all the milestones with excellent results that support further therapeutic development of our product.