Grant: Project Grant

Induced pluripotent stem cells (iPSCs) offer huge potential for regenerative medicine. Being pluripotent, they can be differentiated to any cell or tissue in the body. Pluripotency is one component of stemness; the other is the ability to self-renew. In order to meet the anticipated demand for high quality iPSCs, we have been developing bioprocesses for expanding them as aggregates in computer controlled vessels called stirred suspension bioreactors (imagine a smaller version of an upright washing machine). Recently we made international headlines when we demonstrated that we could generate mouse iPSCs 1000-fold more efficiently in bioreactors compared to static culture. Our research has led us to the discovery of a new phenomenon, mechanopluripotency, wherein mechanical forces caused by bioreactor stirring promote pluripotency. In this project, we plan to study if mechanopluripotency occurs in human iPSCs and if it can be used to improve and standardize hiPSC expansion culture. Our study focuses on the newly characterize naive hiPSCs, which more closely resemble their mouse counterpart. We will determine if mechanopluripotency operates in naïve hiPSCs and by what mechanism. We will determine if mechanopluripotency allows hiPSC expansion without a requirement for pluripotency maintenance factors and chemical inhibitors. This move will not only lower iPSC expansion costs, it will also increase cell quality since inhibitors are suspected to have negative consequences on quality. Finally, we will determine if mechanopluripotency allows the efficient derivation of hiPSCs in bioreactors, a goal which has previously eluded us.