Growth factor-dependent proliferation of the pancreatic beta-cell line betaTC-tet: an assay for beta-cell mitogenic factors

The ability to expand normal pancreatic islet beta cells in culture would significantly advance the prospects of cell therapy for diabetes. A number of growth factors can stimulate limited islet cell replication, however other factors may exist which are more effective beta-cell-specific mitogens. The search for novel beta-cell growth factors has been hampered by the lack of a beta-cell-specific proliferation assay. We developed a simple and sensitive assay for beta-cell growth factors based on a conditionally-transformed mouse beta-cell line (betaTC-tet). These cells express the SV40 T antigen (Tag) oncoprotein under control of the tetracycline (Tc) operon regulatory system. In the presence of Tc, Tag expression is tightly shut off and the cells undergo complete growth arrest. Here we show that the growth-arrested cells can proliferate in response to growth factors in the absence of Tag. Using this assay, a number of growth factors previously shown to be mitogenic to a mixed islet cell population were found to induce proliferation of pure beta cells. We conclude that growth-arrested betaTC-tet cells can be employed in a survey of factors from various sources for identifying novel factors with beta-cell mitogenic activity.