3D cell-based biosensors in drug discovery programs : microtissue engineering for high throughput screening /
William S. Kisaalita.
imprint
Boca Raton : CRC Press, c2010.
description
xvii, 386 p. : ill. ; 25 cm.
ISBN
1420073494 (hardcover : alk. paper), 9781420073492 (hardcover : alk. paper)
format(s)
Book
Holdings
More Details
imprint
Boca Raton : CRC Press, c2010.
isbn
1420073494 (hardcover : alk. paper)
9781420073492 (hardcover : alk. paper)
abstract
"This book is based upon cutting-edge research conducted in the authors lab (Cellular Bioengineering), which over the past decade has developed a number of sophisticated techniques to facilitate use of 3D cell based assays or biosensors. This book uses data from peer-reviewed publications to conclusively justify use of 3D cell cultures in cell-based biosensors (assays) for (HTS). The majority of assays performed in accelerated drug discovery processes are biochemical in nature, but there is a growing demand for live cell-based assays. Unlike biochemical ones, cellular assays are functional approximations of in vivo biological conditions and can provide more biologically relevant information"--Provided by publisher.
catalogue key
7259649
 
Includes bibliographical references and indexes.
A Look Inside
About the Author
Author Affiliation
Dr. Kisaalita presents evidence in support of embracing 3D cell-based systems for widespread use in drug discovery programs. He goes to the root of the issue, establishing the 3D cell-based biosensor physiological relevance by comparing 2D and 3D culture from genomic to functional levels. He then assembles the bioengineering principles behind successful 3D cell-based biosensor systems. Kisaalita also addresses the challenges and opportunities for incorporating 3D cell-based biosensors or cultures in current discovery and pre-clinical development programs. This book makes the case for widespread adoption of 3D cell-based systems, rendering their 2D counterparts, in the words of Dr. Kisaalita, "quaint, if not archaic" in the near future.
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Summaries
Unpaid Annotation
"This book is based upon cutting-edge research conducted in the authors lab (Cellular Bioengineering), which over the past decade has developed a number of sophisticated techniques to facilitate use of 3D cell based assays or biosensors. This book uses data from peer-reviewed publications to conclusively justify use of 3D cell cultures in cell-based biosensors (assays) for (HTS). The majority of assays performed in accelerated drug discovery processes are biochemical in nature, but there is a growing demand for live cell-based assays. Unlike biochemical ones, cellular assays are functional approximations of in vivo biological conditions and can provide more biologically relevant information"--Provided by publisher.
Main Description
Advances in genomics and combinatorial chemistry during the past two decades inspired innovative technologies and changes in the discovery and pre-clinical development paradigm with the goal of accelerating the process of bringing therapeutic drugs to market. Written by William Kisaalita, one of the foremost experts in this emerging field, 3D Cell-Based Biosensors in Drug Discovery Programs: Microtissue Engineering for High Throughput Screening provides the latest information - from theory to practice - on challenges and opportunities for incorporating 3D cell-based biosensors or assays in drug discovery programs.
Main Description
Advances in genomics and combinatorial chemistry during the past two decades inspired innovative technologies and changes in the discovery and pre-clinical development paradigm with the goal of accelerating the process of bringing therapeutic drugs to market. Written by William Kisaalita, one of the foremost experts in this field, 3D Cell-Based Biosensors in Drug Discovery Programs: Microtissue Engineering for High Throughput Screeningprovides the latest information - from theory to practice - on challenges and opportunities for incorporating 3D cell-based biosensors or assays in drug discovery programs. The book supplies a historical perspective and defines the problem 3D cultures can solve. It also discusses how genomics and combinatorial chemistry have changed the way drug are discovered and presents data from the literature to underscore the less-than-desirable pharmaceutical industry performance under the new paradigm. The author uses results from his lab and those of other investigators to show how 3D micro environments create cell culture models that more closely reflect normal in vivo-like cell morphology and function. He makes a case for validated biomarkers for three-dimensionality in vitroand discusses the advantages and disadvantages of promising tools in the search of these biomarkers. The book concludes with case studies of drugs that were abandoned late in the discovery process, which would have been discarded early if tested with 3D cultures. Dr. Kisaalita presents evidence in support of embracing 3D cell-based systems for widespread use in drug discovery programs. He goes to the root of the issue, establishing the 3D cell-based biosensor physiological relevance by comparing 2D and 3D culture from genomic to functional levels. He then assembles the bioengineering principles behind successful 3D cell-based biosensor systems. Kisaalita also addresses the challenges and opportunities for incorporating 3D cell-based biosensors or cultures in current discovery and pre-clinical development programs. This book makes the case for widespread adoption of 3D cell-based systems, rendering their 2D counterparts, in the words of Dr. Kisaalita "quaint, if not archaic" in the near future.
Main Description
This book is based upon cutting-edge research conducted in the author's lab (Cellular Bioengineering), which over the past decade has developed a number of sophisticated techniques to facilitate use of 3D cell based assays or biosensors. This book uses data from peer-reviewed publications to conclusively justify use of 3D cell cultures in cell-based biosensors (assays) for (HTS). The majority of assays performed in accelerated drug discovery processes are biochemical in nature, but there is a growing demand for live cell-based assays. Unlike biochemical ones, cellular assays are functional approximations of in vivo biological conditions and can provide more biologically relevant information.
Bowker Data Service Summary
This text is based upon cutting-edge research conducted in the author's lab (cellular bioengineering), which over the past decade has developed a number of sophisticated techniques to facilitate use of 3D cell based assays or biosensors.
Table of Contents
Prefacep. xv
Authorp. xvii
Introduction
Biosensors and Bioassaysp. 3
Conventional Biosensorsp. 3
Conventional Biosensor Applicationsp. 8
Bioprocess Monitoring and Controlp. 9
Food Quality Controlp. 9
Environmental Monitoringp. 9
Military Biodefense Applicationsp. 12
Clinical Diagnosticsp. 13
Cell-Based Biosensors versus Cell-Based Assays (Bioassays)p. 13
3D Culturesp. 15
Two-Dimensional (2D) Culture Systemsp. 15
3D Culture Systemsp. 18
Tissue Engineering versus Microtissue Engineeringp. 18
Concluding Remarksp. 19
Referencesp. 19
Target-Driven Drug Discoveryp. 23
Drug Discovery and Developmentp. 23
Targetp. 23
Hitp. 23
Leadp. 24
Candidatep. 24
Investigational New Drug (IND) Applicationp. 24
Drug or Productp. 24
The Taxol (Paclitaxel) Discovery Casep. 25
The Gleevec (Imatinib Mesylate) Discovery Casep. 35
Target-Driven Drug Discovery Paradigmp. 43
Genomics and Proteomicsp. 44
Combinatorial Chemistryp. 46
HTS/uHTSp. 47
The New Discovery Paradigm Promisep. 47
Concluding Remarksp. 49
Referencesp. 51
3D versus 2D Cultures
Comparative Transcriptional Profiling and Proteomicsp. 57
Transcriptional Profiling Studiesp. 57
Comparative GO Annotation Analysisp. 60
Proteomics Studiesp. 65
Concluding Remarksp. 67
Referencesp. 74
Comparative Structure and Functionp. 77
Complex Physiological Relevancep. 77
Cardiomyocyte Contractilityp. 78
Cells and Scaffoldp. 78
Comparative Structurep. 78
Comparative Functionp. 79
HTS Application Feasibilityp. 80
Liver Cell Bile Canaliculi In Vitrop. 82
Cells and Scaffoldp. 82
Comparative Structure and Functionp. 83
HTS Application Feasibilityp. 84
Nerve Cell Voltage-Gated Calcium Signalingp. 84
Cells and Scaffoldp. 84
Comparative Structurep. 86
Comparative Functionp. 87
HTS Application Feasibilityp. 89
Concluding Remarksp. 89
Referencesp. 90
Emerging Design Principles
Chemical Microenvironmental Factorsp. 97
Cell Adhesion Moleculesp. 97
Cadherinsp. 97
Selectinsp. 99
The Integrin Superfamilyp. 101
The Ig-Domain-Containing Superfamily of CAMsp. 103
Short-Range Chemistryp. 103
ECM Compositionp. 104
Substrate Surface Chemistryp. 108
Long-Range Chemistryp. 110
Cytokines, Chemokines, Hormones, and Growth Factorsp. 111
Matrix Metalloproteinases (MMPs)p. 112
Concluding Remarksp. 112
Referencesp. 115
Spatial and Temporal Microenvironmental Factorsp. 121
Nano- and Microstructured Surfacesp. 122
Scaffoldsp. 122
Nano and Scaffold-Combined Structuresp. 148
Temporal Factorp. 148
Concluding Remarksp. 153
Referencesp. 160
Material Physical Property and Force Microenvironmental Factorsp. 169
Basicsp. 169
Young's Modulus, Stiffness, and Rigidityp. 169
Shear Modulus or Modulus of Rigidityp. 170
Material Physical Properties Characterizationp. 171
Contractile Force Generation in Cellsp. 177
Force and Geometry Sensingp. 179
Stiffness-Dependent Responsesp. 180
Biological and Nonbiological Materials' Stiffnessp. 180
Stiffness-Dependent Morphology and Adhesionp. 182
Stiffness-Dependent Migrationp. 183
Stiffness-Dependent Growth and Differentiationp. 185
Substrate Stiffness-Dependent Cell's Internal Stiffnessp. 187
Force-Dependent Responsesp. 189
Concluding Remarksp. 193
Referencesp. 198
Proteomics as a Promising Tool in the Search for 3D Biomarkersp. 207
Why Search for Three-Dimensionality Biomarkers?p. 207
Cellular Adhesionsp. 209
Signaling Pathwaysp. 212
Overview of Proteomics Techniquesp. 213
Protein Separation by Two-Dimensional Polyacrylamide Gel Electrophoresis (2DE)p. 213
Peptide Detectionp. 214
Protein Identificationp. 214
Study Design and Methodsp. 215
Addressing Low-Abundance and Poor Solubility Proteinsp. 215
Biomarker Validationp. 216
Concluding Remarksp. 217
Referencesp. 217
Readout Present and Near Futurep. 221
Readout Present and Near Futurep. 221
Fluorescence-Based Readoutsp. 224
Jablonski Diagram and Fluorescence Basicsp. 224
Fluorescence Readout Configurationsp. 225
Bioluminescence-Based Readoutsp. 230
Label-Free Biosensor Readoutsp. 235
Impedancep. 235
Surface Plasmon Resonancep. 242
Concluding Remarksp. 245
Referencesp. 246
Ready-to-Use Commercial 3D Platesp. 253
Introductionp. 253
Algimatrix™p. 254
Fabricationp. 254
Complex Physiological Relevancep. 255
Unique Featuresp. 256
Extracel™p. 257
Synthesisp. 257
Complex Physiological Relevancep. 257
Unique Featuresp. 257
Ultra-Web™p. 259
Fabricationp. 260
Complex Physiological Relevancep. 260
Unique Featuresp. 261
Market Opportunitiesp. 262
The Opportunityp. 262
Potential Customersp. 262
Market Sizep. 263
Market Size Estimationp. 263
Concluding Remarksp. 264
Referencesp. 265
Technology Deployment Challenges and Opportunities
Challenges to Adopting 3D Cultures in HTS Programsp. 269
Typical HTS Laboratory and Assay Configurationsp. 269
Just-in-Time Reagents Provision Modelp. 274
Limited Value-Addition from 3D Culture Physiological Relevance: Transepithelium Drug Transport and Induction of Drug Metabolizing Enzyme Casesp. 276
Transepithelium Drug Transport: Caco-2 Assayp. 276
Induction of Drug Metabolizing Enzymes: Hepatocyte Assaysp. 283
Paucity of Conclusive Support of 3D Culture Superiorityp. 283
Referencesp. 285
Cases for 3D Cultures in Drug Discoveryp. 289
Three Casesp. 289
The ß1-Integrin Monoclonal Antibody Casep. 289
Integrinsp. 289
Monoclonal Antibodiesp. 290
Experimental System: Breast Cancer Cells in Matrigelp. 293
Treatment with ß1-Integrin Inhibitory Antibody Reduced Malignancy in In Vitro-3D and In Vivo, but Not in In Vitro-2D Systemsp. 293
The Matrix Metalloproteinase Inhibitors Casep. 294
Extracellular Matrix Metalloproteinases (MMPs)p. 294
MMP Inhibitors (MMPIs)p. 295
Experimental System: Fibrosarcoma Cells in Collagen Gelsp. 295
Treatment with Pericellular Proteolysis Inhibitors in 3D Cultures and In Vivo Did Not Prevent Cell Migration or Metastasisp. 296
Resistance to the Chemotherapeutic Agents Casep. 297
Experimental System: Multicellular Tumor Spheroid (MCTS)p. 297
MCTS More Accurately Approximate In Vivo Resistance to Chemotherapeutic Agentsp. 298
Concluding Remarksp. 300
Referencesp. 301
Ideal Case Study Designp. 307
Rationale for the Case Studyp. 307
Why Hepatotoxicity?p. 308
Morphology of the Liverp. 308
What Is Hepatotoxicity?p. 308
Hepatotoxicity and hESC-Derived Hepatocyte-Like Cellsp. 310
Two Reasons Why IADRs Have Attracted Proposed Studiesp. 310
IADRs and Mitochondrial Inner Transmembrane Potential (¿¿m)p. 314
Study Design and Methodsp. 317
Experimental Design and Rationalep. 317
Cell Culture and Drug Exposurep. 318
Expression of Drug-Metabolizing Enzymesp. 318
Alanine Aminotransferase (ATL) Activity Assayp. 318
Mitochondrial Membrane Potential (¿¿m) Measurementp. 318
Analysis and Expected Resultsp. 319
Quality Assessment of HTS Assaysp. 319
Expected Resultsp. 319
Potential Pitfallsp. 320
Referencesp. 320
Patents for 3D Scaffoldsp. 323
Referencesp. 328
Current Drug Targetsp. 331
Popular Cell Lines in Drug Discoveryp. 357
HEK 293p. 357
Backgroundp. 357
Morphology and Ploidyp. 358
CHOp. 358
Backgroundp. 358
Morphology and Ploidyp. 358
HeLap. 358
Backgroundp. 358
Morphology and Ploidyp. 359
HepG2p. 359
Backgroundp. 359
Morphology and Ploidyp. 360
U2OSp. 360
Backgroundp. 360
Morphology and Ploidyp. 360
COS-7/CV-1p. 360
Backgroundp. 360
Morphology and Ploidyp. 361
Referencesp. 361
Stem Cells in Drug Discoveryp. 363
Referencesp. 368
Indexp. 373
Company Indexp. 385
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