Metabolomic Signatures of Pluripotent Cell Lines
Stem cells are the hope for many people suffering from some form of organ or tissue dysfunction. The renowned capacity of stem cells and their ability to give rise to multiple types of adult cells (pluripotent) makes them so appealing for cell therapies. Stem cells originally derived from early embryos, often referred to us, as embryonic stem (ES) cells. They have extensive growth potential, self-replication capacity, can mature into adult cells, and hence can reconstitute damaged tissue when are injected to the organism. When isolated from early embryos, ES cells can be maintained in a dish under specific conditions without loosing their ability to expand indefinitely. A critical requirement for maintenance of ES cells in cultures is a layer of murine cells that supply unidentified signals vital to the ES cells. This requirement, obviously involves a risk for clinical therapies. Therefore, there is considerable effort ongoing by many investigators to define these factors. When needed, ES cells can be removed from the murine cell layer and spontaneously and without the ability to control it, can form all adult tissues. This event occurs in a very disorganized way resulting in “monster” tumors. Intensive investigation controlling the fate of the cells still is undergoing. In this project, we are suggesting to identify and characterize the factors that are differentiating ES cells from their murine layer cells, and from their matured cells. The main goal is to control the factors that are responsible to their pluripotentacy, and enriched the factors that are participating in the maturation of the cells. In order to get matured functional cells, particularly liver cells.
Controlling maturation of ES cells into active matured liver cells is proposed as ideal technique for end-stage liver diseases, because their ability to expand extensively, differentiate into all mature liver cells, and reconstitute liver tissue when transplanted. In this project, we are proposing to analyze and identify factors that are differentiating cells in their embryonic stem state from cells that were already committed to liver cells. In a three well designed specific aims, we are suggesting to examine changes in factors within ES cells before and after they have committed to differentiate into liver cells as a function of time and culture conditions. With state of the art technologies and an interdisciplinary research teams this project goals are to be compliance with the highest medical and ethical standards.
This proposed project is directly relevant to the mission of proposition 71 and specifically will benefit the State of California and its citizens in the following ways:
A. The knowledge and data from this project will directly improve the California health care system and reduce the long-term health care cost burden on California through the development of therapies that treat disease and injuries with the ultimate goal to cure them.
B. The knowledge and data from the proposed project will specifically provide opportunity for the state of California to benefit from royalties, patents and licensing fees that result from this project.
C. This project will benefit the state of California economy by creating jobs and projects to its citizens, will generate millions of dollars in new tax revenues to the state.
D. The knowledge and data from this project potentially will advance biotech industry in the state of California
E. This project will benefit the scientists, researchers and medical doctors working on this specific project by bringing them to a world-class recognition and leadership in the stem cell research.