Since the introduction of recombinant human growth hormone and insulin a quarter century ago, protein therapeutics has greatly broadened the ho- zon of health care. Many patients suffering with life-threatening diseases or chronic dysfunctions, which were medically untreatable not long ago, can attest to the wonder these drugs have achieved. Although the ?rst generation of p- tein therapeutics was produced in recombinant Escherichia coli, most recent products use mammalian cells as production hosts. Not long after the ?rst p- duction of recombinant proteins in E. coli, it was realized that the complex tasks of most post-translational modi?cations on proteins could only be ef?ciently carried out in mammalian cells. In the 1990s, we witnessed a rapid expansion of mammalian-cell-derived protein therapeutics, chie?y antibodies. In fact, it has been nearly a decade since the market value of mammalian-cell-derived protein therapeutics surpassed that of those produced from E. coli. A common characteristic of recent antibody products is the relatively large dose required for effective therapy, demanding larger quantities for the treatment of a given disease. This, coupled with the broadening repertoire of protein drugs, has rapidly expanded the quantity needed for clinical applications. The increasing demand for protein therapeutics has not been met exclusively by construction of new manufacturing plants and increasing total volume capacity. More - portantly the productivity of cell culture processes has been driven upward by an order of magnitude in the past decade.

Offers a comprehensive overview of cell culture engineering, providing insight into cell engineering, systems biology approaches and processing technology In Cell Culture Engineering: Recombinant Protein Production, editors Gyun Min Lee and Helene Faustrup Kildegaard assemble top class authors to present expert coverage of topics such as: cell line development for therapeutic protein production; development of a transient gene expression upstream platform; and CHO synthetic biology. They provide readers with everything they need to know about enhancing product and bioprocess attributes using genome-scale models of CHO metabolism; omics data and mammalian systems biotechnology; perfusion culture; and much more. This all-new, up-to-date reference covers all of the important aspects of cell culture engineering, including cell engineering, system biology approaches, and processing technology. It describes the challenges in cell line development and cell engineering, e.g. via gene editing tools like CRISPR/Cas9 and with the aim to engineer glycosylation patterns. Furthermore, it gives an overview about synthetic biology approaches applied to cell culture engineering and elaborates the use of CHO cells as common cell line for protein production. In addition, the book discusses the most important aspects of production processes, including cell culture media, batch, fed-batch, and perfusion processes as well as process analytical technology, quality by design, and scale down models. -Covers key elements of cell culture engineering applied to the production of recombinant proteins for therapeutic use -Focuses on mammalian and animal cells to help highlight synthetic and systems biology approaches to cell culture engineering, exemplified by the widely used CHO cell line -Part of the renowned "Advanced Biotechnology" book series Cell Culture Engineering: Recombinant Protein Production will appeal to biotechnologists, bioengineers, life scientists, chemical engineers, and PhD students in the life sciences.

This book is the culmination of three decades of accumulated experience in teaching biotechnology professionals. It distills the fundamental principles and essential knowledge of cell culture processes from across many different disciplines and presents them in a series of easy-to-follow, comprehensive chapters. Practicality, including technological advances and best practices, is emphasized. This second edition consists of major updates to all relevant topics contained within this work. The previous edition has been successfully used in training courses on cell culture bioprocessing over the past seven years. The format of the book is well-suited to fast-paced learning, such as is found in the intensive short course, since the key take-home messages are prominently highlighted in panels. The book is also well-suited to act as a reference guide for experienced industrial practitioners of mammalian cell cultivation for the production of biologics.

Consolidating and expanding current, fundamental notions of virology and animal cell cultivation, this practical reference examines the development of insect cell culture techniques for the production of recombinant proteins and insect pathogenic viruses.;Resolving on-the-job problems such as sparging cell damage and reduced infectivity cells, Insect Cell Culture Engineering: includes special introductory material as well as background information on insect pathogenic viruses, the molecular biology of baculoviruses and bioreactor design; offers advice on how to save time when deciding which insect cell line, bioreactor and medium to exploit; discusses the preparation of mathematical modelling in animal cell culture; addresses the concerns associated with insect cell immobilization and the use of serum-free culture media; provides insights into the protective effects of polymer additives and insect cell gene expression in pharmaceutical research; and analyzes process scale-up and reactor design.;Bridging the gap between laboratory research and pilot plant scale insect culture/baculovirus technology, Insect Cell Culture Engineering is designed as a reference for biochemical and bioprocess engineers, bioprocess technologists, biochemists, molecular and cell biologists, microbiologists, and upper-level undergraduate and graduate students in these disciplines.

Step-by-step, practical guidance for the acquisition, manipulation,and use of cell sources for tissue engineering Tissue engineering is a multidisciplinary field incorporatingthe principles of biology, chemistry, engineering, and medicine tocreate biological substitutes of native tissues for scientificresearch or clinical use. Specific applications of this technologyinclude studies of tissue development and function, investigatingdrug response, and tissue repair and replacement. This area israpidly becoming one of the most promising treatment options forpatients suffering from tissue failure. Written by leading experts in the field, Culture of Cellsfor Tissue Engineering offers step-by-step, practicalguidance for the acquisition, manipulation, and use of cell sourcesfor tissue engineering. It offers a unique focus on tissueengineering methods for cell sourcing and utilization, combiningtheoretical overviews and detailed procedures. Features of the text include: Easy-to-use format with a two-part organization Logically organized—part one discusses cell sourcing,preparation, and characterization and the second part examinesspecific engineered tissues Each chapter covers: structural and functional properties oftissues, methodological principles, culture, cellselection/expansion, cell modifications, cell seeding, tissueculture, analytical assays, and a detailed description ofrepresentative studies End-of-chapter features include useful listings of sources forreagents, materials, and supplies, with the contact details of thesuppliers listed at the end of the book A section of elegant color plates to back up the figures in thechapters Culture of Cells for Tissue Engineering givesnovice and seasoned researchers in tissue engineering an invaluableresource. In addition, the text is suitable for professionals inrelated research, particularly in those areas where cell and tissueculture is a new or emerging tool.

It is my privilege to contribute the foreword for this unique volume entitled: “Plant Tissue Culture Engineering,” edited by S. Dutta Gupta and Y. Ibaraki. While there have been a number of volumes published regarding the basic methods and applications of plant tissue and cell culture technologies, and even considerable attention provided to bioreactor design, relatively little attention has been afforded to the engineering principles that have emerged as critical contributions to the commercial applications of plant biotechnologies. This volume, “Plant Tissue Culture Engineering,” signals a turning point: the recognition that this specialized field of plant science must be integrated with engineering principles in order to develop efficient, cost effective, and large scale applications of these technologies. I am most impressed with the organization of this volume, and the extensive list of chapters contributed by expert authors from around the world who are leading the emergence of this interdisciplinary enterprise. The editors are to be commended for their skilful crafting of this important volume. The first two parts provide the basic information that is relevant to the field as a whole, the following two parts elaborate on these principles, and the last part elaborates on specific technologies or applications.

Transcriptome Analysis, by Frank Stahl, Bernd Hitzmann, Kai Mutz, Daniel Landgrebe, Miriam Lübbecke, Cornelia Kasper, Johanna Walter und Thomas Scheper Transcriptome Data Analysis for Cell Culture Processes, by Marlene Castro-Melchor, Huong Le und Wei-Shou Hu Modeling Metabolic Networks for Mammalian Cell Systems: General Considerations, Modeling Strategies, and Available Tools, by Ziomara P. Gerdtzen Metabolic Flux Analysis in Systems Biology of Mammalian Cells, by Jens Niklas und Elmar Heinzle Advancing Biopharmaceutical Process Development by System-Level Data Analysis and Integration of Omics Data, by Jochen Schaub, Christoph Clemens, Hitto Kaufmann und Torsten W. Schulz Protein Glycosylation and Its Impact on Biotechnology, by Markus Berger, Matthias Kaup und Véronique Blanchard Protein Glycosylation Control in Mammalian Cell Culture: Past Precedents and Contemporary Prospects, by Patrick Hossler Modeling of Intracellular Transport and Compartmentation, by Uwe Jandt und An-Ping Zeng Genetic Aspects of Cell Line Development from a Synthetic Biology Perspective, by L. Botezatu, S. Sievers, L. Gama-Norton, R. Schucht, H. Hauser und D. Wirth.

The completion of the Human Genome Project and the rapid progress in cell bi- ogy and biochemical engineering, are major forces driving the steady increase of approved biotech products, especially biopharmaceuticals, in the market. Today mammalian cell products (“products from cells”), primarily monoclonals, cytokines, recombinant glycoproteins, and, increasingly, vaccines, dominate the biopharmaceutical industry. Moreover, a small number of products consisting of in vitro cultivated cells (“cells as product”) for regenerative medicine have also been introduced in the market. Their efficient production requires comprehensive knowledge of biological as well as biochemical mammalian cell culture fundamentals (e.g., cell characteristics and metabolism, cell line establishment, culture medium optimization) and related engineering principles (e.g., bioreactor design, process scale-up and optimization). In addition, new developments focusing on cell line development, animal-free c- ture media, disposables and the implications of changing processes (multi-purpo- facilities) have to be taken into account. While a number of excellent books treating the basic methods and applications of mammalian cell culture technology have been published, only little attention has been afforded to their engineering aspects. The aim of this book is to make a contribution to closing this gap; it particularly focuses on the interactions between biological and biochemical and engineering principles in processes derived from cell cultures. It is not intended to give a c- prehensive overview of the literature. This has been done extensively elsewhere.

Bioreactors: Animal Cell Culture Control for Bioprocess Engineering presents the design, fabrication, and control of a new type of bioreactor meant especially for animal cell line culture. The new bioreactor, called the "see-saw bioreactor," is ideal for the growth of cells with a sensitive membrane. The see-saw bioreactor derives its name from its principle of operation in which liquid columns in either limb of the reactor alternately go up and down. The working volume of the reactor is small, to within 15 L. However, it can easily be scaled up for large production in volume of cell mass in the drug and pharmaceutical industries. The authors describe the principle of operation of the see-saw bioreactor and how to automatically control the bioprocess. They discuss different control strategies as well as the thorough experimental research they conducted on this prototype bioreactor in which they applied a time delay control for yield maximization. To give you a complete understanding of the design and development of the see-saw bioreactor, the authors cover the mathematical model they use to describe the kinetics of fermentation, the genetic algorithms used for deriving the optimal time trajectories of the bioprocess variables, and the corresponding control inputs for maximizing the product yield. One chapter is devoted to the application of time delay control. Following a description of the bioreactor’s working setup in the laboratory, the authors sum up their investigation and define the future scope of work in terms of design, control, and software sensors.

Maintaining quality of life in an ageing population is one of the great challenges of the 21st Century. This book summarises how this challenge is being met by multi-disciplinary developments of specialty biomaterials, devices, artificial organs and in-vitro growth of human cells as tissue engineered constructs.Biomaterials, Artificial Organs and Tissue Engineering is intended for use as a textbook in a one semester course for upper level BS, MS and Meng students. The 25 chapters are organized in five parts: Part one provides an introduction to living and man-made materials for the non-specialist; Part two is an overview of clinical applications of various biomaterials and devices; Part three summarises the bioengineering principles, materials and designs used in artificial organs; Part four presents the concepts, cell techniques, scaffold materials and applications of tissue engineering; Part five provides an overview of the complex socio-economic factors involved in technology based healthcare, including regulatory controls, technology transfer processes and ethical issues. - Comprehensive introduction to living and man-made materials - Looks at clinical applications of various biomaterials and devices - Bioengineering principles, materials and designs used in artificial organs are summarised