Heart failure is the major cause of death in the U.S., and heart defects are the major cause of death in infants. This project will design, build and validate a device that can be used at a hospital to create living heart tissue for repair of failing hearts and heart defects. Clinicians would inject a patient's own cells into the device, which would then automatically control the release of chemicals required to make living heart muscle. In about 2 weeks, surgeons would open the device, remove the heart muscle, and use it to restructure a failing or malformed heart. This technology could transform the clinical approach to heart disease and heart defects, and could produce the first regenerative cure for these conditions.
The implementation of novel and transformative therapies using cardiac tissue derived from induced pluripotent stem cells (iPSC) requires the development of new technologies that can efficiently create heart tissue from pluripotent stem cells and ensure elimination of tumorigenic undifferentiated cells without laboratory intervention or extensive processing. This can be accomplished with a closed bioreactor system to create engineered cardiac tissue from iPSC. The intellectual merit of this proposal is based on the hypothesis that a bioreactor containing a pump, heart matrix-based hydrogel, and nanoparticles controlling the timed release of differentiation factors can create a 3-D contractile cardiac tissue with organization and function similar to native tissue. To test this hypothesis, a closed-system bioreactor that pumps media through cardiac matrix hydrogels along with silica nanoparticles that release cardiac differentiation factors will be constructed and tested with human iPSC. The release of factors shown to eliminate pluripotent cells will purify the tissue and prevent the implantation of tumorigenic cells and this will be verified through PCR and immunostaining. Finally, tissues with suturable scaffolds will be generated and implanted into a rat model of cardiac defect repair. The broader educational and social impacts of this proposal are integrated with the intellectual merit and include outreach activities with several Houston high schools though the Rice K-12 Initiative to bring increased awareness of biotechnology, biomaterials and stem cells among high school students and increased participation of high school students in science & engineering.
