Cell Physiology Online Journals

 Cell culture and cell lines have assumed an important role in studying physiological, pathophysiological, and differentiation processes of specific cells. It allows the examination of stepwise alterations in the structure, biology, and genetic makeup of the cell under controlled environments. This is especially valuable for complex tissues, such as the pancreas, which is composed of various cell types, where in vivo examination of individual cells is difficult, if not impossible. The extreme difficulties in the isolation and purification of individual epithelial cells from complex tissues by maintaining their native characteristics have hampered our understanding of their physiological, biological, growth, and differentiation characteristics. Attempts have been made to culture almost every tissue, including neuronal cells, bone, cartilage, and hair cells. In general, animal cells, particularly fibroblasts, can be more successfully cultured than human cells, and human fibroblasts are easier to culture than epithelial cells. Also, different epithelial cells show different responses to culture conditions. Despite advances in culturing techniques, human epithelial cells could not be maintained in culture for long time periods. The problem is the tendency of human cells to undergo senescence after a certain cell division. Transfection of these cells with the E6E7 gene of human papilloma virus 16, or with the small and large T antigen of the simian virus 40, has partially overcome the senescence and has increased cell longevity in vitro but has not led to immortality of the cells. The resulting genetic manipulations limit the use of these cells for molecular biological studies, especially for defining genetic changes that occur during cell differentiation and transformation. The introduction of these foreign genes alters the function of the host’s regulatory genes including the inactivation of the tumor suppressor protein p53 and retinoblastoma protein pRb. Even though these cell lines do not grow in soft agar, which would be a first sign of transformation, or when introduced into nude mice, the additional transfection with certain oncogenes such as k-ras has resulted in the malignant transformation of the cells.

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