3-D cell-based biosensors in drug discovery programs : microtissue engineering for high throughput screening / by William S. Kisaalita. — Boca Raton, Fla. : CRC ; London : Taylor & Francis [distributor], 2010. – (63.3034/K61) |
Contents
Contents
Preface xv
Author xvii
PART I Introduction
Chapter 1 Biosensors and Bioassays 3
1.1 Conventional Biosensors 3
1.2 Conventional Biosensor Applications 8
1.3 Cell-Based Biosensors versus Cell-Based Assays (Bioassays) 13
1.4 3D Cultures 15
1.5 Concluding Remarks 19
References 19
Chapter 2 Target-Driven Drug Discovery 23
2.1 Drug Discovery and Development 23
2.2 The Taxol (Paclitaxel) Discovery Case 25
2.3 The Gleevec (Imatinib Mesylate) Discovery Case 35
2.4 Target-Driven Drug Discovery Paradigm 43
2.5 The New Discovery Paradigm Promise 47
2.6 Concluding Remarks 49
References 51
PART II 3D versus 2D Cultures
Chapter 3 Comparative Transcriptional Profiling and Proteomics 57
3.1 Transcriptional Profiling Studies 57
3.2 Comparative GO Annotation Analysis 60
3.3 Proteomics Studies 65
3.4 Concluding Remarks 67
References 74
Chapter 4 Comparative Structure and Function 77
4.1 Complex Physiological Relevance
4.2 Cardiomyocyte Contractility
4.3 Liver Cell Bile Canaliculi In Vitro 82
4.4 Nerve Cell Voltage-Gated Calcium Signaling 84
4.5 Concluding Remarks 89
References 90
PART III Emerging Design Principles
Chapter 5 Chemical Microenvironmental Factors 97
5.1 Cell Adhesion Molecules 97
5.2 Short-Range Chemistry
5.3 Long-Range Chemistry
5.4 Concluding Remarks
References
Chapter 6 Spatial and Temporal Microenvironmental Factors 121
6.1 Nano-and Microstructured Surfaces 122
6.2 Scaffolds 122
6.3 Nano and Scaffold-Combined Structures 148
6.4 Temporal Factor 148
6.5 Concluding Remarks 153
References 160
Chapter 7 Material Physical Property and Force Microenvironmental Factors 169
7.1 Basics 169
7.2 Stiffness-Dependent Responses 180
7.3 Force-Dependent Responses 189
7.4 Concluding Remarks 193
References 198
Chapter 8 Proteomics as a Promising Tool in the Search for 3D Biomarkers 207
8.1 Why Search for Three-Dimensionality Biomarkers? 207
8.2 Cellular Adhesions 209
8.3 Signaling Pathways 212
8.4 Overview of Proteomics Techniques 213
8.5 Study Design and Methods 215
8.6 Concluding Remarks 217
References 217
Chapter 9 Readout Present and Near Future 221
9.1 Readout Present and Near Future 221
9.2 Fluorescence-Based Readouts 224
9.3 Bioluminescence-Based Readouts 230
9.4 Label-Free Biosensor Readouts 235
9.5 Concluding Remarks 245
References 246
Chapter 10 Ready-to-Use Commercial 3D Plates 253
10.1 Introduction 253
10.2 Algimatrix 254
10.3 Extracel 257
10.4 Ultra-Web 259
10.5 Market Opportunities 262
10.6 Concluding Remarks 264
References 265
PART IV Technology Deployment Challenges and Opportunities
Chapter 11 Challenges to Adopting 3D Cultures in HTS Programs 269
11.1 Typical HTS Laboratory and Assay Configurations 269
11.2 Just-in-Time Reagents Provision Model 274
11.3 Limited Value-Addition from 3D Culture Physiological Relevance: Transepithelium Drug Transport and Induction of Drug Metabolizing Enzyme Cases 276
11.4 Paucity of Conclusive Support of 3D Culture Superiority 283
References 285
Chapter 12 Cases for 3D Cultures in Drug Discovery 289
12.1 Three Cases
12.2 The β1-Integrin Monoclonal Antibody Case
12.3 The Matrix Metalloproteinase Inhibitors Case
12.4 Resistance to the Chemotherapeutic Agents Case 297
12.5 Concluding Remarks 300
References 301
Chapter 13 Ideal Case Study Design 307
13.1 Rationale for the Case Study 307
13.2 Why Hepatotoxicity? 308
13.3 Hepatotoxicity and hESC-Derived Hepatocyte-Like Cells 310
13.4 Study Design and Methods 317
13.5 Analysis and Expected Results 319
References 320
Appendix A Patents for 3D Scaffolds 323
References 328
Appendix B Current Drug Targets 331
Appendix C Popular Cell Lines in Drug Discovery 357
C1 HEK 293 357
C1.1 Background 357
C1.2 Morphology and Ploidy 358
C2 CHO 358
C2.1 Background 358
C2.2 Morphology and Ploidy 358
C3 HeLa 358
C3.1 Background 358
C3.2 Morphology and Ploidy 359
C4 HepG2 359
C4.1 Background 359
C4.2 Morphology and Ploidy 360
C5 U2OS 360
C5.1 Background 360
C5.2 Morphology and Ploidy 360
C6 COS-7/CV-1 360
C6.1 Background 360
C6.2 Morphology and Ploidy 361
References 361
Appendix D Stem Cells in Drug Discovery 363
References 368
Index 373
Company Index 385