Designer Cells Derived from Primary Tissue and Designed Cell Lines as a Sustainable Cell Source for Drug Discovery and Safety Assessment 177

Volker Sandig and Ingo Jordan

7.1 Introduction 177

7.2 Suitability and Limitations of Primary Cells as Physiologic Models 178

7.3 Tumor Cell Lines: Sometimes an Alternative 179

7.4 Immortalization by Design: Infinite Proliferation and a Differentiated Phenotype? 179

7.4.1 Telomerase: the Primary Target in Human Cells 179

7.4.2 Inactivation of Rb and p53 Pathways 181

7.4.3 Conditional Immortalization 183

7.5 Designed Cells in Complex Drug Tests 184

7.5.1 Cell Properties Required for Complex Screening Systems 184

7.5.2 Complex Designer Cells in Screens 185

7.5.3 Viruses and Host Cells in Drug Tests 189

7.5.4 Viruses and Designed Host Cells 190

7.5.5 Defined Viral and Cellular Pathways and Designed Host Cells 190

7.5.6 Virus Field Isolates and Designed Host Cells 192

7.5.7 Designed Viruses and Designed Host Cells 193

7.5.8 Designed Host Cells Combined 194 References 196

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