A novel protein delivery platform to promote stem cell reprogramming and differentiation
Previous work has attempted to use recombinant protein to make useful pluripotent stem cells such as induced pluripotent stem cells. However, due to protein degradation in cultures or inside the cells, the efficiency of making such kind of stem cells is extremely low beyond any practical use. Our research team has recently developed a novel nanotechnology to manufacture protein capsules containing recombinant proteins including OCT4, SOX2, KLF4, and C-MYC (OSKM). These protein capsules will allow optimal intracellular delivery of capsulated proteins. Nanocapsulated recombinant proteins are much stable in culture media and much efficient for intracellular delivery. Therefore, we expect to use this novel technology to improve protein delivery into cells. With this technology, we can efficiently make useful stem cells for future clinical applications. By the same technology, we can promoter neuronal cell differentiation from human stem cells, thus achieving a large quantity of neural cells for cell transplantation and drug screening purpose. The success of our research project will allow us to efficiently make patient specific stem cells and neural cells. This is important for cell replacement therapy in neural repair and in drug discovery. Our proposal research will be an important step to translate stem cell research into future clinical applications.
Stem cell transplantation has emerged as a method that may improve recovery of many human diseases such as neurodegenerative disorders (Parkinson's disease and Alhzeimer's disease) and brain injuries. Studies of stem cell transplantation have been limited because the source of transplantable brain cells is limited. Recent technology demonstrated that induced pluripotent stem cells could be a feasible source for patient specific stem cells. However, current technology is limited in the derivation of clinically useful stem cells. We have recently found that a new method to introduce proteins into cells, thus paving the way to promote the generation of induced pluripotent stem cells. The experiments in this grant will devise a new method to promote stem cell derivation as well as enrich for the useful brain cells differentiated from pluripotent stem cells. These results are applicable to the treatment of many neurological disorders such as Parkinsons, Alzheimer’s and Huntington’s diseases. Our proposed research will accelerate the pace in the application of human embryonic stem cells and induced pluripotent stem cells for neural repair, thus benefiting the health care of the State of California and its citizens.