Maintenance of an undifferentiated state of human induced pluripotent stem cells through migration-dependent regulation of the balance between cell-cell and cell-substrate interactions.

We present an outlook on the current strategies for maintaining and culturing human induced pluripotent stem cells (hiPSCs) in an undifferentiated state without affecting their pluripotency. First, cell structures and function are described in relation to interactions between hiPSCs and their surroundings. Second, the phenomenon of spontaneous deviation from undifferentiated hiPSCs in cultures with feeder cells is addressed, with a summary of current topics that are of particular interest to our studies. The key regulatory factors that can contribute to the growth and maintenance of undifferentiated hiPSCs are also discussed, with a summary of recent work toward a culture strategy to control hiPSC fate through balancing cell-cell and cell-substrate interactions. Finally, we discuss culture process design in our previous studies with respect to maintaining and expanding cultures of undifferentiated and pluripotent hiPSCs. We focus on the regulation of migration-dependent balance between cell-cell and cell-substrate interactions. This review offers novel insights into the regulation and processing of stem cells for research in regenerative medicine.