Control of Mammalian Cell Proliferation as an Important Strategy in Cell Culture Technology, Cancer Therapy and Tissue Engineering

Abstract

In the last decades research on the molecular basis of proliferation and cell-cycle control was mainly motivated by curiosity to understand this complex regulatory network which orchestrates the global changes of cycling cells in a temporal and spatial manner. Based on such mechanistic research, cell-cycle regulatory circuits came to be perceived as a fundamental program which stands at the center of multicellular life, since the cell-cycle machinery integrates several important decisions on a cell’s fate such as apoptosis, differentiation and growth. Consequently, cell-cycle control systems are important for cell homeostasis and, when defective, can lead to uncontrolled proliferation and neoplastic growth. Cell-cycle regulatory networks have certainly become a focus in cancer therapy for control of carcinogenic growth and the elimination of neoplastic cells. The bioengineering community remained relatively unaffected by theses key developments in the field of proliferation control and continued to use indefinitely growing, neoplastic cells as their workhorse for biopharmaceutical manufacturing. Only recently, as a more refined picture of cell-cycle regulatory systems emerged from basic research, long-standing critical issues in cell culture technology such as apoptosis, protein production, cell differentiation and growth in serum- and protein-free media have been addressed by metabolic engineering and process development strategies using mammalian cells.