Pharmaceutical Applications of Cell and Tissue Culture to Drug Transport, 1991 NATO Science Series A: Series, Vol. 218

In recent years there have been rapid advances in the growth and differentiation of mammalian cells in culture. This has led to increasing use of such in vitro systems in a wide variety of studies on fundamental aspects of cell structure and function, including normal growth and metabolism, mechanisms of differentiation and oncogenesis, mechanisms of protein and membrane synthesis and cell polarity. Recent advances in our ability to grow cells, including human cells, on permeable supports, to generate confluent cellular barriers with the morphological polarity corresponding to their in vivo counterparts has greatly facilitated such studies. In particular these new techniques have led to an increasing interest in the use of cell and tissue culture systems as a means for examining the transport of drugs across epithelial and endothelial barriers. An obvious question is whether these new in vitro methodologies will provide convenient systems that can substitute for and replace animal models. Various research groups both in academia and in the pharmaceutical industry have been investigating these types of methodologies in order to develop convenient well characterized systems that can be used to examine basic aspects of transcellular transport and to evaluate the permeability of drug molecules and delivery systems. Of particular note is use of confluent cell layers to study the transport of large molecules such as peptides and proteins produced through recombinant DNA technology.

Pharmaceutical Applications of Cell Culture: An Overview.- Growth and Characterization of Cell and Tissue Cultures for the Study of Drug Transport.- Differentiation of Human Colon Cancer Cells.- Criteria for Evaluating and Choosing a Relevant Cell Line.- Use of Fabricated Living Tissue and Organ Equivalents as Defined Higher Order Systems for the Study of Pharmacologic Responses to Test Substances.- Intracellular Pathways; Exocytic and Endocytic Routes Relying upon Selective Vesicular Transport.- Carrier-Mediated Transport of Bile Acids and Amino Acids in Caco-2 Cells.- Passive Absorption of Drugs in Caco-2 Cells.- Receptor-Mediated Transport of Cobalamin in Caco-2 Cells: Intracellular Localization of Transcobalamin II.- An in Vitro Absorption Model System Based on Cell Monolayers (Intestine 407, MDBK).- Transferrin Endocytosis and Fluid Phase Uptake in the Differentiable Intestinal Cell Line HT-29.- Culture of Human Goblet Cells.- Endothelial Barriers.- Transport of Drugs Across the Blood-Brain Barrier: In Vitro and in Vivo Strategies.- Metabolism of Catecholamine Prodrugs by Cultured Bovine Brain Microvessel Endothelial Cells.- Membrane Recycling, Adsorptive and Receptor-Mediated Endocytosis by Primary Bovine Cerebral Microvessel Endothelial Cell Monolayers in Vitro.- Lipoproteins and Reconstituted Blood-Brain Barrier.- Regulation of the Myocardial Blood Supply by Adenosine and Adenine Nucleotides: Consequences of Newly Detected Barrier Functions of the Coronary Endothelium.- Cultured Human Umbilical Vascular Endothelial Cells and Their Underlying Matrix as Models to Study Cell Adhesion.- Human Nasal Epithelial Cultures.- Experimental Models for Buccal and Sublingual Drug Absorption Including Epithelial Cell Multilayers and Monolayers.- Effect of Culture Environment on Terminal Differentiation of Human Epidermal Keratinocytes.- Human Keratinocyte Cell Lines.- Regulation of Haemopoietic Cell Development.- Multilineage Hematopoietic Expression in a Three-Dimensional Long Term Bone Marrow Culture System.- Isolation, Culturing and in Vitro Activation of Liver Macrophages.- In Vitro Evaluation of Macrophage Mediated Host Defenses against Neoplastic Disease.- Microcarrier-Facilitated Cultures for Fibroblastic and Epithelial Cells.- Strategies for Immortalising Human Primary Cells and the Steps That Lead to Immortality.- Carcinogen Metabolism in Immortalised Human Cells Grown as Hybrid Cells in Culture.- Application of Cell and Tissue Culture in the Pharmaceutical Industry?.- Key Issues in the Use of Cell and Tissue Culture Systems.- Photograph of Participants.- Participants.