The Study of Tissue Culture Cells Uncovers Cell Cycle Regulation in Mammals

Cell cycle regulation in human cells is more complex than in other non-mammalian systems. To understand this increased level of complexity, and to understand the cell cycle alterations that are the cause of cancer, it is important to study the cell cycle not only in model organisms, but also in human cells. Researchers use normal or tumor cells grown in plastic dishes to study the properties of the human cell cycle, a method called tissue culture or cell culture. It is, however, important to note that many of the cell types used to study the human cell cycle have altered cell cycle properties due to genetic alterations that occurred during their culturing or because they were isolated from human tumors. Furthermore, in vitro culture conditions do not resemble those found in the organism and could lead to altered behavior of cells. Although some aspects of mammalian cell division are not recapitulated in cell culture conditions—such as tissue organization and developmental signals governing cell cycle control—cell culture systems nevertheless provide critical insights into the mammalian cell’s intrinsic mechanisms governing cell division. Researchers are also working toward establishing culture systems that more closely resemble the cell architecture in tissues. For example, polymer lattices are currently being developed that allow scientists to grow cells in three-dimensional culture mimicking cellular organization within a tissue.

Primary human cells and other mammalian cells have a finite life span when cultured in vitro. Normal human cells, for example, divide 25–50 times, but thereafter proliferation slows and eventually stops. This process is called replicative senescence. Some cells can escape this process and become immortalized, allowing researchers to establish cell lines. Although these cell lines harbor genetic alterations that affect some aspects of their proliferation, they are nevertheless a useful tool for studying cell cycle progression in human cells. These cell lines provide an inexhaustible supply of cells that, as we will see next, can be manipulated to progress through the cell cycle in a synchronous manner, allowing for the analysis of protein levels and enzymatic activity at different stages of the cell cycle.