Learning Materials in Biosciences
Learning Materials in Biosciences textbooks compactly and concisely discuss a specific biological, bio-
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Cornelia Kasper
Verena Charwat
Antonina Lavrentieva
Editors
Cell Culture
Technology
Editors
Cornelia Kasper Verena Charwat
Department of Biotechnology Department of Biotechnology
University of Natural Resources & Life University of Natural Resources & Life
Sciences Sciences
Vienna, Austria Vienna, Austria
Antonina Lavrentieva
Institute for Technical Chemistry
Gottfried Wilhelm Leibniz Universität
Hannover, Germany
ISSN 2509-6125 ISSN 2509-6133 (electronic)
Learning Materials in Biosciences
ISBN 978-3-319-74853-5 ISBN 978-3-319-74854-2 (eBook)
https://doi.org/10.1007/978-3-319-74854-2
Library of Congress Control Number: 2018946536
© Springer International Publishing AG, part of Springer Nature 2018
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V
Preface
Cell culture technology has rapidly evolved over the past half century and thus cannot be
“limited” any more to the classical fermentation and animal production cell line culture
technologies. Nowadays, methods comprise also of modern 3D techniques for cell
expansion and/or differentiation. The approaches for tissue engineering and cell-based
therapies have woken the demand of cultivation strategies beyond standard cell culture
methods. These include the development and establishment of suitable protocols for cul-
tivating cells – especially primary cells – under physiological conditions.
This textbook is structured into 10 different chapters: brief history of the developments
in mammalian cell culture technology until today including stem cell cultivation; intro-
duction to relevant equipment and consumable materials as well as standard techniques
used in cell culture labs; outline on requirements, developments, and current status in
media design; summary of tumor cell line and tissue cultivation; introduction of 3D
culture techniques for tissue engineering and cell-based testing systems; overview on
relevant biomaterials and their characteristics; demonstration of mechanisms and effects
involved in cell-surface interaction; definition and discussion on physiological condi-
tions with focus on oxygen in cell culture procedures; overview on different co-culture
systems; and an introduction to suitable strategies for automation of cell culture proce-
dures.
This textbook is a unique collection of chapters relevant for modern cell culture technol-
ogy, providing an excellent overview of the “essentials” and the current paradigms, as
well as insights into relevant methods underlying modern cell culture technology. The
chapters are based on lectures and teaching material of the authoring teams, thus making
the textbook excellently suitable for teaching and to support bachelor, master, and doc-
toral theses.
Notwithstanding, if the reader already has experience in mammalian cell culture, or he
or she is a novice to this field, this book will be a valuable reading, which will deepen
knowledge and expand the understanding how modern cell culture works.
We thank all authors of this book who in addition to their daily chores and academic
work helped us with their brilliant and outstanding contributions.
Antonina Lavrentieva
Hannover, Germany
Cornelia Kasper
Vienna, Austria
June 2018
VII
Contents
1 Cell Culture Bioprocess Technology: Biologics and Beyond............................. 1
Sofie O’Brien, Yonsil Park, Samira Azarin, and Wei-Shou Hu
2 Essentials in Cell Culture.......................................................................................................... 23
Antonina Lavrentieva
3 Cell Culture Media........................................................................................................................ 49
Reinhard Henschler
4 Establishment of Tumor Cell Lines: From Primary Tumor
Cells to a Tumor Cell Line......................................................................................................... 61
Katharina Meditz and Beate Rinner
5 The Third Dimension in Cell Culture:
From 2D to 3D Culture Formats........................................................................................... 75
Verena Charwat and Dominik Egger
6 Biomaterials...................................................................................................................................... 91
Rainer Detsch, Julia Will, Jasmin Hum, Judith A. Roether,
and Aldo R. Boccaccini
7 Cell–Surface Interactions......................................................................................................... 107
Megan Livingston and F. Kurtis Kasper
8 Mimicking Physiological Oxygen in Cell Cultures................................................... 129
Nicholas R. Forsyth, Rachel Steeg, Muhammad Ahmad, Mohammed Al Zubaidi,
Rakad Al-Jumaily, Marwan Merkhan, and Tina Dale
9 Co-cultures........................................................................................................................................ 139
Roland Jacobs and Ralf Hass
10 Automation of Cell Culture Processes............................................................................. 155
Jan Hansmann, Ivo Schwedhelm, Andreas Clementi, Dominik Egger,
and Cornelia Kasper
Contributors
Muhammad Ahmad Andreas Clementi
Guy Hilton Research Centre Department of Biotechnology, University of
Institute of Science and Natural Resources and Life Science
Technology in Medicine Vienna, Austria
Keele University, Stoke on Trent, UK
[email protected][email protected] Tina Dale
Guy Hilton Research Centre, Institute of Science
Mohammed Al Zubaidi
and Technology in Medicine, Keele University
Guy Hilton Research Centre, Institute of
Stoke on Trent, UK
Science and Technology in Medicine
[email protected]Keele University
Stoke on Trent, UK Rainer Detsch
[email protected] Institute of Biomaterials, Department of
Materials Science and Engineering
Rakad Al-Jumaily University of Erlangen-Nuremberg
Guy Hilton Research Centre, Institute of Erlangen, Germany
Science and Technology in Medicine
[email protected]Keele University
Dominik Egger
Stoke on Trent, UK
Department of Biotechnology, University of
[email protected] Natural Resources and Life Science
Vienna, Austria
Samira Azarin
[email protected]Department of Chemical Engineering
Nicholas R. Forsyth
and Materials Science
Guy Hilton Research Centre, Institute of Science
University of Minnesota
and Technology in Medicine, Keele University
Minneapolis, MN, USA
Stoke on Trent, UK
[email protected] [email protected]Aldo R. Boccaccini Jan Hansmann
Institute of Biomaterials, Department of Department Tissue Engineering and
Materials Science and Engineering Regenerative Medicine (TERM)
University of Erlangen-Nuremberg University Hospital Wuerzburg
Erlangen, Germany Wuerzburg, Germany
[email protected] [email protected] Ralf Hass
Verena Charwat Biochemistry and Tumor Biology Lab,
Department of Biotechnology, University of Department of Obstetrics and Gynecology
Natural Resources & Life Sciences Hannover Medical School
Vienna, Austria Hannover, Germany
[email protected] [email protected]
IX
Contributors
Reinhard Henschler Katharina Meditz
Blood Transfusion Services SRC Division of Biological Research
Zürich/Chur, Switzerland Medical University of Graz
[email protected] Graz, Austria
[email protected]Wei-Shou Hu
Department of Chemical Engineering and Marwan Merkhan
Materials Science, University of Minnesota Guy Hilton Research Centre, Institute of Science
Minneapolis, MN, USA and Technology in Medicine, Keele University
[email protected] Stoke on Trent, UK
[email protected]Jasmin Hum
Institute of Biomaterials, Department of
Sofie O’Brien
Materials Science and Engineering
Department of Chemical Engineering and
University of Erlangen-Nuremberg
Materials Science, University of Minnesota
Erlangen, Germany
Minneapolis, MN, USA
[email protected] [email protected]Roland Jacobs
Yonsil Park
Department of Clinical Immunology and
Department of Chemical Engineering and
Rheumatology, Hannover Medical School
Materials Science, University of Minnesota
Hannover, Germany
Minneapolis, MN, USA
[email protected] [email protected]Cornelia Kasper
Department of Biotechnology, University of Beate Rinner
Natural Resources and Life Science Division of Biological Research
Vienna, Austria Medical University of Graz
[email protected] Graz, Austria
Division of Biomedical Research, Core Facility
F. Kurtis Kasper
Alternative Biomodels and Preclinical Imaging
Department of Orthodontics, The University of
Graz, Austria
Texas Health Science Center at Houston
[email protected]School of Dentistry
Houston, TX, USA
Judith A. Roether
[email protected] Institute of Biomaterials, Department of
Materials Science and Engineering
Antonina Lavrentieva
University of Erlangen-Nuremberg
Institute of Technical Chemistry
Erlangen, Germany
Leibniz University Hannover
[email protected]Hannover, Germany
[email protected] Ivo Schwedhelm
Department Tissue Engineering and
Megan Livingston
Regenerative Medicine (TERM)
Department of Orthodontics, The University of
University Hospital Wuerzburg
Texas Health Science Center at Houston,
Wuerzburg, Germany
School of Dentistry
[email protected]Houston, TX, USA
[email protected] X Contributors
Rachel Steeg Julia Will
Guy Hilton Research Centre, Institute of Science Institute of Biomaterials, Department of
and Technology in Medicine, Keele University Materials Science and Engineering
Stoke on Trent, UK University of Erlangen-Nuremberg
[email protected] Erlangen, Germany
[email protected] XI
Abbreviations
AFM Atomic force microscopy EPO Erythropoietin
AIA Activation-induced apoptosis ESCs Embryonic stem cells
ALS Amyotrophic lateral sclerosis ETO Ethylene oxide
APCs Antigen-presenting cells
Asn Asparagine FACS Fluorescence-activated cell sorting
ATMPs Advanced therapy medicinal FAD Flavin adenine dinucleotide
products FBS Fetal bovine serum
ATP Adenosine triphosphate FDA Food and Drug Administration
FEM Finite element method
BAL Bioartificial liver FGF Fibroblast growth factor
BG Bioactive glasses FLIM Fluorescence lifetime imaging
BHK Baby hamster kidney microscopy
BMP Bone morphogenetic protein FMD Foot-and-mouth disease
BrdU Bromodeoxyuridine FRET Förster resonance energy transfer
CAD Computer-aided design G6PD Glucose-6-phosphate
CAR-T cells Chimeric antigen receptor T cells dehydrogenase
CD Cluster of differentiation G-CSF Granulocyte colony-stimulating
factor
CFSE Carboxyfluorescein succinimidyl
ester GCP Good clinical practice
CO2 Carbon dioxide GFP Green fluorescent protein
CoC Ceramic-on-ceramic GMP Good manufacturing practice
CFU Colony forming units GOI Gene of interest
CHO Chinese hamster vary GVHD Graft-versus-host disease
μCT/nCT Micro-/nano-computer tomography
HA Hydroxyapatite
DAPI 4′,6-Diamidino-2-phenylindole HBSS Hank’s buffered salt solution
DHFR Dihydrofolatreduktase HEPES 4-(2-Hydroxyethyl)-1-pipera-
zineethanesulfonic acid
DMEM Dulbecco’s Modified Eagle Medium
HFB Hollow fiber bioreactors
DMSO Dimethyl sulfoxide
HPV Human papilloma virus
DNA Deoxyribonucleic acid
HPL Human platelet lysate
rDNA Recombinant DNA
HSCs Hematopoietic stem cells
DO Dissolved oxygen
DPN Diphosphopyridine nucleotide
ICM Inner cell mass
IL Intraluminal
EBV Epstein-Barr virus
iPSCs Induced pluripotent stem cells
ECM Extracellular matrix
IMDM Iscove’s Modified Dulbecco’s
EDTA Ethylenediaminetetraacetic acid
Medium
EL Extra-luminal
ITS Insulin-transferrin-sodium selenite
ELISA Enzyme-linked immunosorbent
assay
LC-MS Liquid chromatography–mass
EMEM Eagle’s Minimum Essential Medium spectrometry
EPI Epiblast LCL Lymphoblastoid cell lines
XII Abbreviations
LCST Lower critical solution PSCs Pluripotent stem cells
temperature tPA Tissue plasminogen activator
LDH Lactate dehydrogenase PMMA Poly(methyl methacrylate)
PVC Polyvinyl chloride
Mab Monoclonal antibody
MACS Magnetic bead-associated cell RNA Ribonucleic acid
sorting
RPMI Roswell Park Memorial Institute
MEF Mouse embryonic fibroblasts
MHC Major histocompatibility SCID Severe combined
complex immunodeficient
MLC Mixed lymphocyte culture SDS Sodium dodecyl sulfate
MLR Mixed lymphocyte reaction SEM Scanning electron microscopy
MoM Metal-on-metal Ser Serine
MRI Magnetic resonance imaging scFv Single-chain variable fragment
MSCs Mesenchymal stem cells, SCF Stem cell factor
mesenchymal stromal cells
STR Short tandem repeat
MTT 3-(4,5-Dimethylthiazol-2-yl)-
2,5-diphenyltetrazolium bromide
TAA Tumor-associated antigen
TCP Tricalcium phosphate
NK Natural killer
TE Tissue engineering
NSCs Neural stem cells
hTERT Human telomerase reverse
transcriptase
O2 Oxygen
TGF Transforming growth factor
OCTGT Office of Cellular, Tissue, and
Gene Therapies TME Tumor microenvironment
TPN Triphosphopyridine nucleotide
PBMC Peripheral blood mononuclear cell TPO Thrombopoietin
PBS Phosphate-buffered saline
PE Polyethylene UV Ultraviolet
PGE2 Prostaglandin E2
VEGF Vascular endothelial growth
PGM Phosphoglucomutase
factor
PID controller Proportional-integral-derivative
controller
WST Water soluble tetrazolium
PrE Primitive endoderm
7AAD 7-Aminoactinomycin
PI Propidium iodide
2D Two-dimensional
PCR Polymerase chain reaction
3D Three-dimensional
PS Polystyrene
