Pluripotent stem cells have the potential to treat a variety of human diseases, including diabetes, cardiovascular diseases, Parkinson’s diseases and Alzheimer’s diseases, in cell replacement therapies. Human embryos are the main sources for producing human pluripotent stem cells that are genetically unmodified so far. Alternative methods for producing pluripotent stem cells include somatic cell nuclear transfer or therapeutic cloning, which needs unfertilized or newly fertilized eggs, and has been experiencing both ethical and technical difficulties. Recent progress in reprogramming by retroviral transduction of a cocktail of four transcription factors offers a solution to these problems because no embryos or eggs are needed in this system. However, the use of retroviral transduction represents a serious hurdle to the use of these induced pluripotent stem cells for therapeutic application, because retroviral transduction can cause activation of cancer-inducing genes and are therefore risky.
The goal of this research is to create new pluripotent stem cells that are genetically unmodified by inducing endogenous pluripotency regulators using small molecules. Screening for small molecules that induce endogenous pluripotency factors to replace retroviral delivery of reprogramming factors will allow safer production of customized patient-specific stem cells from patient’s own somatic cells and open up new avenues into stem cell therapies. It will make the dream of stem cell-based therapies come true in the foreseeable future.
Statement of Benefit to California:
The establishment of pluripotent stem cell lines opened a new era in biomedical research. Human pluripotent stem cells provide great hope to be used in cell replacement therapy for a variety of human diseases. The derivation and propagation of new lines of human pluripotent stem cells from somatic sources using small molecules will allow production of patient- and disease- specific stem cells in a safe and efficient manner. These virus-free pluripotent stem cells will have important research and clinical application for understanding, diagonosing and treating serious injury and diseases that Californians may suffer. Californians will therefore benefit tremendously from the outcome of the proposed research. In addition, the development of new methods to derive genetically unmodified human pluripotent stem cells that do not require the use of either human embryos or eggs will reduce the ethical concerns of Californians for stem cell research and will stimulate other stem cell-related research in California. This research will undoubtedly bring enormous benefits for California.