Nonmitogenic survival-enhancing autocrine factors including cyclophilin A contribute to density-dependent mouse embryonic stem cell growth.

An improved understanding of the role of extracellular factors in controlling the embryonic stem cell (ESC) phenotype will aid the development of cell-based therapies. While the role of extracellular factors in controlling the pluripotency and differentiation of embryonic stem cells (ESCs) has been the subject of much investigation, the identity and role of extrinsic factors in modulating ESC growth under conditions supporting self-renewal remain largely unknown. We demonstrate that mouse ESC (mESC) growth is density dependent and that one of the mechanisms underlying this phenomenon is the action of survival-enhancing autocrine factors. Proteomic analysis of proteins secreted by mouse ESCs demonstrates significant levels of cyclophilin A which increases the growth rate of mouse ESCs in a dose-dependent manner. Additionally, inhibition of the cyclophilin A receptor CD147 decreases the growth rate of mESCs. These findings identify cyclophilin A as a novel survival-enhancing autocrine factor in mouse ESC cultures.