Cellular and Molecular Determinants of Pluripotency and Stability
hESCs are pluripotent cells that can be maintained indefinitely in culture. These characteristics have led to much enthusiasm for their potential use in cell-replacement therapies. One obstacle to realizing this potential is the incomplete knowledge of mechanisms involved regulating pluripotent fate decisions including survival, self-renewal and stability. While hESCs can be maintained in vitro, cells grown in continuous culture have been shown to develop aberrations associated with cancer in vivo. Therefore it is the goal of this work to determine the mechansims that regulate pluripotent stem cell growth without giving rise to abnormal stem cells with the potential for tumor formation.
Pluripotent stem cells (PSCs) have the potential to revolutinize medicine for use in cell-based therapies. However, the translational use of hESCs will not be realized unless we understand how pluripotency is regulated in these cells. Defining how pluripotency is controlled could improve our ability to derive new cell lines in a more controlled conditions. This could enhance California as a recognized world leader in PSC research through the generation of a centralized and comprehensive resource of PSC lines with potential clinical use. This work will also create jobs to support this effort, and validate the decision of California voters who ensured the passage of Proposition 71. Our proposal to improve our understanding of PSC pluripotency and stability will make treatment strategies from hESCs one-step closer.