Early Translational I
ICOC Funds Committed:
In 2007, there was great excitement in both the general and scientific communities when it was announced that it had been discovered how to "reprogram" adult cells into a state almost indistinguishable from true embryonic stem cells. These cells were named induced pluripotent stem cells, or iPS. The public was appropriately excited about the possibility of retaining all the potentials benefits of embryonic stem cells, without the need for destruction of embryos. The scientific world immediately saw the possibilities of iPS including the generation of patient-specific and disease-specific pluripotent cell lines, and the possibility of deriving non-immunogenic ("self") replacement cells for diseased and degenerative post-natal organs. The original iPS were produced by using a virus to introduce the necessary four genes into cells to reprogram them. However, cells changed in this way could never be re-introduced into a human because it is not safe to do so. Another method for introducing the effect of these genes must be found as a pre-requisite to their clinical use. The current proposal is an idea which may be an effective solution to this bottleneck in the path of iPS from the science laboratory to a potential human treatment. Instead of using virus vectors to introduce the genes, the necessary factors are engineered so that part of the protein is recognized by the cells and carried to the nucleus. In this way, the factors can exert their effect, without causing permanent changes to the DNA of the cell (as the viral method does). If this proposed technique is successful, there implications are very large. The ability to safely reprogram adult cells into a "stem cell" state has the potential to transform transplantation medicine, by supplying a readily available source of "self" cells that may be potentially used as replacement cells for diseased or degenerative organs.
Statement of Benefit to California:
Pluripotent stem cells have the potential to transform medicine, because of the possbilit to regenerate diseased or degenerative organs. This is because pluripotent cells retain the capability to become any type of specialized adult cell (for example nerve cell, muscle cell, skin cell etc), through a process known as differentiation. Until recently, the only source of such cells was a human embryo, but very recently it was discovered how to induce normal adult cells to return to this state - so called "induced pluripotent stem cells". The current proposal describes a plausible variation on the method to produce induced pluripotent stem cells that makes them much safer for eventual therapeutic use. (In brief, the new method dispenses with the need for laboratory viruses to deliver the genes into the cell necessary to generate the induced pluripotent stem cells). Potentially such pluripotent cells might be used to derive cells for the treatment of progressive and degenerative diseases once thought incurable. For example diseases such as Parkinson's disease and Alzheimer's disease might be alleviated by producing new neurons, type I diabetes by producing new insulin-producing pancreatic cells, or heart failure by producing new cardiac muscle cells, and delivering them into the respective diseased organs. Another enormous potential benefit to the citizens of California, is the possibility of producing disease-specific stem cells. These cells would be a great research tool for investigating causes and treatments of many diseases in the laboratory. In addition to the potential benefits to humankind, any treatments discovered would likely lead to development of new Californian companies and Californian jobs.