The objective of this proposal is to create a novel neural stem cell (NSC) delivery system that will ultimately improve efficacy of the NSC transplantation into brain for brain tissue regeneration. The system will not only passively protect NSCs from immune attack, but also actively stimulate NSC survival and differentiation under hypoxic condition, a typical condition at the transplantation site. NSC therapy holds a great potential to treat brain diseases. However, direct NSC transplantation often results in a high rate of cell death, caused primarily by host immune attack and hypoxic condition at the transplantation site. A potential engineering solution is to use a biomaterial-based NSC delivery system to protect the transplanted cells. Yet, the efficacy of this approach is limited due to inefficient immunoprotection, limited cell-biomaterial interaction, and hypoxic condition. The proposed work will address these issues by encapsulating NSCs in immunoprotection capsules that will effectively block both immune proteins and pro-inflammatory cytokines. The capsules will also possess a microenvironment to stimulate the differentiation of NSCs into neurons. To actively stimulate NSC survival under hypoxic condition, cells will be continuously oxygenated.
The proposed studies will generate broader impacts on cell transplantation for disease treatment and foster three levels of education and outreach activities. Technically, the research has the potential to advance the current design strategy for cell transplantation systems and significantly improve efficacy of cell transplantation-based disease treatment. It also enables a multifaceted education and outreach plan, including exposing high school students to polymers and biotechnologies; engaging high school female students in science and engineering; and providing underrepresented/minority graduate students with solid training in the biotechnology field and will educate a new generation of biomedical scientists and engineers.
