Development of non integrating gene delivery system for reprogramming adult cells and identify molecules to enhance reprogramming efficiency

Funding Type: 
Tools and Technologies I
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Embryonic stem cells have great potentials in the future of medicine and research because they can develop into virtually any kind of tissue type and potentially become an unlimited resource for cell therapy. However, the ethical issue surrounding the use of embryonic stem cells comes from the fact that they are derived from human embryos in a process that causes the death of the embryos. In 2006, scientists reported that stem cells can be created without eggs or embryos by using viruses to deliver four regulator genes, a process called induced pluripotent stem cells (iPSC). However, before iPS cells can be used in the clinic, many technical problems need to be overcome, such as eliminating the use of viruses or inserting regulator genes into the genome that potentially can cause cancer. Here we propose to develop a non integrating system to deliver the regulator genes which can be turned off after cells have been reprogrammed. This delivery system will enable researchers to introduce genes into the cells, switch them on during the reprogramming period, and turn off once cells have been reprogrammed. This method does not integrate genes into the cell's genome and thus, preventing additional changes in the host's genome. In addition, another technical difficulty to reprogram cells is that the process is very inefficient. Scientists have reported the success rate of 0.1-5% of obtaining iPS cells. We will be screening for molecules that will enhance the reprogramming process. Reprogramming adult stem cells into induced pluripotent stem cells could generate a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine. However, before reprogrammed cells can be used in the clinic, they must be grown in conditions are free of any animal origin. We will perform and adapt reprogramming of cells in defined serum free medium containing enhancing molecules identified in this study to generate iPS cell lines that will be suitable for clinical studies.

Statement of Benefit to California: 

Stem cells have potential in many areas of medical research, such as they offer the possibility of renewable sources of replacement cells and new tissues to treat many kinds of diseases, conditions, and disabilities. However, the use of stem cells has been very controversial due to the fact that they are derived from human embryos. The recent discovery of transforming adult cells back to the equivalent of embryonic state without the use of eggs or embryos will open a new era of research in cell-based therapy and tissue engineering. Before reprogrammed cells can be used in the clinic, there are some technical hurdles need to be overcome, such as the use of viral vectors to deliver genes and introducing regulator genes that can cause cancer. We propose to develop a novel delivery method that does not insert genes into the cell's genome and enables genes to be turned on and off, thus preventing genes to be expressed and potentially cause cancer after cells have been reprogrammed. In addition, in order to obtain large number of reprogrammed cells for cell therapy, the reprogramming process needs to be more robust than the current state of obtaining between 0.1-5% reprogramming efficiency. We will screen for molecules and examine their ability to enhance reprogramming efficiency. Finally, we will generate iPS cells using techniques developed in this study and adapt them to animal origin free medium which will be applicable for clinical studies. Results from our research will increase the statue of California's research and benefit its citizens by enhancing the process of creating patient-specific pluripotent stem cells that can be used for disease research and cell replacement therapies.