Cornelia Kasper - Böcker

This textbook shall introduce the students to 3D cell culture approaches and applications. An overview on existing techniques and equipment is provided and insight into various aspects and challenges that researchers need to consider and face during culture of 3D cells is given.The reader will learn the importance of physiological cell, tissue and organ models and gains important knowledge on 3D analytics.This textbook deepens selected aspects of the textbook “Cell Culture Technology”, which also is published in this series, while offering extended insight into 3D cell culture. The concept of the textbook encompasses various lectures ranging from basics in cell cultivation, tissue engineering, biomaterials and biocompatibility, in vitro test systems and regenerative medicine. The textbook addresses Master- and PhD students interested and/or working in the field of modern cell culture applications and will support the understanding of theessential strategies in 3D cell culture and waken awareness for the potentials and challenges of this application.

This textbook provides an overview on current cell culture techniques, conditions, and applications specifically focusing on human cell culture. This book is based on lectures, seminars and practical courses in stem cells, tissue engineering, regenerative medicine and 3D cell culture held at the University of Natural Resources and Life Sciences Vienna BOKU and the Gottfried Wilhelm Leibniz University Hannover, complemented by contributions from international experts, and therefore delivers in a compact and clear way important theoretical, as well as practical knowledge to advanced graduate students on cell culture techniques and the current status of research.The book is written for Master students and PhD candidates in biotechnology, tissue engineering and biomedicine working with mammalian, and specifically human cells.It will be of interest to doctoral colleges, Master- and PhD programs teaching courses in this area of research.

The editors of this special volume would first like to thank all authors for their excellent contributions. We would also like to thank Prof. Dr. Thomas Scheper, Dr. Marion Hertel and Ulrike Kreusel for providing the opportunity to compose this volume and Springer for organizational and technical support. Tissue engineering represents one of the major emerging fields in modern b- technology; it combines different subjects ranging from biological and material sciences to engineering and clinical disciplines. The aim of tissue engineering is the development of therapeutic approaches to substitute diseased organs or tissues or improve their function. Therefore, three dimensional biocompatible materials are seeded with cells and cultivated in suitable systems to generate functional tissues. Many different aspects play a role in the formation of 3D tissue structures. In the first place the source of the used cells is of the utmost importance. To prevent tissue rejection or immune response, preferentially autologous cells are now used. In particular, stem cells from different sources are gaining exceptional importance as they can be differentiated into different tissues by using special media and supplements. In the field of biomaterials, numerous scaffold materials already exist but new composites are also being developed based on polymeric, natural or xenogenic sources. Moreover, a very important issue in tissue en- neering is the formation of tissues under well defined, controlled and reprod- ible conditions. Therefore, a substantial number of new bioreactors have been developed.

The editors of this special volume would first like to thank all authors for their excellent contributions. We would also like to thank Prof. Dr. Thomas Scheper, Dr. Marion Hertel and Ulrike Kreusel for providing the opportunity to compose this volume and Springer for organizational and technical support. Tissue engineering represents one of the major emerging fields in modern b- technology; it combines different subjects ranging from biological and material sciences to engineering and clinical disciplines. The aim of tissue engineering is the development of therapeutic approaches to substitute diseased organs or tissues or improve their function. Therefore, three dimensional biocompatible materials are seeded with cells and cultivated in suitable systems to generate functional tissues. Many different aspects play a role in the formation of 3D tissue structures. In the first place the source of the used cells is of the utmost importance. To prevent tissue rejection or immune response, preferentially autologous cells are now used. In particular, stem cells from different sources are gaining exceptional importance as they can be differentiated into different tissues by using special media and supplements. In the field of biomaterials, numerous scaffold materials already exist but new composites are also being developed based on polymeric, natural or xenogenic sources. Moreover, a very important issue in tissue en- neering is the formation of tissues under well defined, controlled and reprod- ible conditions. Therefore, a substantial number of new bioreactors have been developed.

Alternative Sources of Adult Stem Cells: Human Amniotic Membrane, by S. Wolbank, M. van Griensven, R. Grillari-Voglauer, and A. Peterbauer-Scherb; *Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical and Tissue Engineering Applications, by P. Moretti, T. Hatlapatka, D. Marten, A. Lavrentieva, I. Majore, R. Hass and C. Kasper; *Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells, by J. W. Kuhbier, B. Weyand, C. Radtke, P. M. Vogt, C. Kasper and K. Reimers; *Induced Pluripotent Stem Cells: Characteristics and Perspectives, by T. Cantz and U. Martin; *Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology, by D. Pei, J. Xu, Q. Zhuang, H.-F. Tse and M. A. Esteban; *Production Process for Stem Cell Based Therapeutic Implants: Expansion of the Production Cell Line and Cultivation of Encapsulated Cells, by C. Weber, S. Pohl, R. Poertner, P. Pino-Grace, D. Freimark, C. Wallrapp, P. Geigle and P. Czermak;*Cartilage Engineering from Mesenchymal Stem Cells, by C. Goepfert, A. Slobodianski, A.F. Schilling, P. Adamietz and R. Poertner;*Outgrowth Endothelial Cells: Sources, Characteristics and Potential Applications in Tissue Engineering and Regenerative Medicine, by S. Fuchs, E. Dohle, M. Kolbe, C. J. Kirkpatrick;*Basic Science and Clinical Application of Stem Cells in Veterinary Medicine, by I. Ribitsch, J. Burk, U. Delling, C. Geißler, C. Gittel, H. Jülke, W. Brehm;*Bone Marrow Stem Cells in Clinical Application: Harnessing Paracrine Roles and Niche Mechanisms, by R. M. El Backly, R. Cancedda;*Clinical Application of Stem Cells in the Cardiovascular System, C. Stamm, K. Klose, Y.-H. Choi

Alternative Sources of Adult Stem Cells: Human Amniotic Membrane, by S. Wolbank, M. van Griensven, R. Grillari-Voglauer, and A. Peterbauer-Scherb; *Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical and Tissue Engineering Applications, by P. Moretti, T. Hatlapatka, D. Marten, A. Lavrentieva, I. Majore, R. Hass and C. Kasper; *Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells, by J. W. Kuhbier, B. Weyand, C. Radtke, P. M. Vogt, C. Kasper and K. Reimers; *Induced Pluripotent Stem Cells: Characteristics and Perspectives, by T. Cantz and U. Martin; *Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology, by D. Pei, J. Xu, Q. Zhuang, H.-F. Tse and M. A. Esteban; *Production Process for Stem Cell Based Therapeutic Implants: Expansion of the Production Cell Line and Cultivation of Encapsulated Cells, by C. Weber, S. Pohl, R. Poertner, P. Pino-Grace, D. Freimark, C. Wallrapp, P. Geigle and P. Czermak;*Cartilage Engineering from Mesenchymal Stem Cells, by C. Goepfert, A. Slobodianski, A.F. Schilling, P. Adamietz and R. Poertner;*Outgrowth Endothelial Cells: Sources, Characteristics and Potential Applications in Tissue Engineering and Regenerative Medicine, by S. Fuchs, E. Dohle, M. Kolbe, C. J. Kirkpatrick;*Basic Science and Clinical Application of Stem Cells in Veterinary Medicine, by I. Ribitsch, J. Burk, U. Delling, C. Geißler, C. Gittel, H. Jülke, W. Brehm;*Bone Marrow Stem Cells in Clinical Application: Harnessing Paracrine Roles and Niche Mechanisms, by R. M. El Backly, R. Cancedda;*Clinical Application of Stem Cells in the Cardiovascular System, C. Stamm, K. Klose, Y.-H. Choi

The Cell-Surface Interaction, by J. S. Hayes, E. M. Czekanska and R. G. Richards. Studying Cell-Surface Interactions In Vitro: A Survey of Experimental Approaches and Techniques, by Stefanie Michaelis, Rudolf Robelek and Joachim Wegener. Harnessing Cell-Biomaterial Interactions for Osteochondral Tissue Regeneration, by Kyobum Kim, Diana M. Yoon, Antonios G. Mikos and F. Kurtis Kasper. Interaction of Cells with Decellularized Biological Materials, by Mathias Wilhelmi, Bettina Giere and Michael Harder. Evaluation of Biocompatibility Using In Vitro Methods: Interpretation and Limitations, by Arie Bruinink and Reto Luginbuehl. Artificial Scaffolds and Mesenchymal Stem Cells for Hard Tissues, by Margit Schulze and Edda Tobiasch. Bioactive Glass-Based Scaffolds for Bone Tissue Engineering, by Julia Will, Lutz-Christian Gerhardt and Aldo R. Boccaccini. Microenvironment Design for Stem Cell Fate Determination, by Tali Re’em and Smadar Cohen. Stem Cell Differentiation Depending on Different Surfaces, by Sonja Kress, Anne Neumann, Birgit Weyand and Cornelia Kasper. Designing the Biocompatibility of Biohybrids, by Frank Witte, Ivonne Bartsch and Elmar Willbold. Interaction of Cartilage and Ceramic Matrix, by K. Wiegandt, C. Goepfert, R. Pörtner and R. Janssen. Bioresorption and Degradation of Biomaterials, by Debarun Das, Ziyang Zhang, Thomas Winkler, Meenakshi Mour, Christina I. Günter, Michael M. Morlock, Hans-Günther Machens and Arndt F. Schilling.

Prospective Isolation and Characterization of Human Bone Marrow-Derived MSCs, by A. Harichandan, K. Sivasubramaniyan, H.-J. BühringUrine as a Source of Stem Cells, by Christina Benda, Ting Zhou, Xianming Wang, Weihua Tian, Johannes Grillari, Hung-Fat Tse, Regina Grillari-Voglauer, Duanqing Pei, Miguel A. Esteban Expansion of Mesenchymal Stem/Stromal Cells under Xenogenic-Free Culture Conditions, by Sven Kinzebach, Karen Bieback Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications, by Danielle Minteer, Kacey G Marra, J Peter Rubin Potential for Osteogenic and Chondrogenic Differentiation of MSC, by Antonina Lavrentieva, Tim Hatlapatka, Anne Neumann, Birgit Weyand, Cornelia Kasper Potential for Neural Differentiation of Mesenchymal Stem Cells, by Letizia Ferroni, Chiara Gardin, Ilaria Tocco, Roberta Epis, Alessandro Casadei, Vincenzo Vindigni, Giuseppe Mucci, Barbara Zavan Migratory Properties of Mesenchymal Stem Cells, by Thomas Dittmar, Frank EntschladenDissecting Paracrine Effectors for Mesenchymal Stem Cells, by Stefania Bruno, Federica Collino, Ciro Tetta, Giovanni Camussi Proteomics Approaches in the Identification of Molecular Signatures of Mesenchymal Stem Cells, by Yin Xiao, Jiezhong ChenDoes the Adult Stroma Contain Stem Cells?, by Richard Schäfer

Engineered MSCs from Patient-Specific iPS Cells, by Irina Eberle, Mohsen Moslem, Reinhard Henschler, Tobias Cantz Fate of Intravenously Injected Mesenchymal Stem Cells and Significance for Clinical Application, by Beate Wagner, Reinhard Henschler The Implications of Stem Cell Applications for Diseases of the Respiratory System, by Mei Ling Lim, Philipp Jungebluth, Paolo Macchiarini Potential of Mesenchymal Stem Cell Applications in Plastic and Reconstructive Surgery, by Birgit Weyand, Peter M. Vogt General Principles for the Regeneration of Bone and Cartilage, by Michael Jagodzinski, C. Haasper Adult Mesenchymal Stem Cells Explored in the Dental Field, by K. M. Fawzy El-Sayed, C. Dörfer, F. Fändrich, F. Gieseler, M. H. Moustafa, H. Ungefroren Mesenchymal Stem Cell Therapy and Lung Diseases, by Khondoker M. Akram, Sohel Samad, Monica Spiteri, Nicholas R. Forsyth Mesenchymal Stem Cells as Cellular Immunotherapeutics in Allogeneic Hematopoietic Stem Cell Transplantation, by Claudia Papewalis, Daniela Topolar, Barbara Götz, Stefan Schönberger, Dagmar Dilloo New Cell-Based Therapy Paradigm: Induction of Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells into Pro-Inflammatory MSC1 and Anti-inflammatory MSC2 Phenotypes, by Aline M. Betancourt Interactions Between Mesenchymal Stem Cells and Dendritic Cells, by Grazia Maria Spaggiari, Lorenzo Moretta MSC and Tumors: Homing, Differentiation, and Secretion Influence Therapeutic Potential, by Naomi D’souza, Jorge Sans Burns, Giulia Grisendi, Olivia Candini, Elena Veronesi, Serena Piccinno, Edwin M. Horwitz, Paolo Paolucci, Pierfranco Conte, Massimo Dominici Sources of Mesenchymal Stem Cells: Current and Future Clinical Use, by Michela Pozzobon, Martina Piccoli, Paolo De Coppi Role of the EU Framework in Regulation of Stem Cell-Based Products, by Giovanni Migliaccio, Cristina Pintus

Prospective Isolation and Characterization of Human Bone Marrow-Derived MSCs, by A. Harichandan, K. Sivasubramaniyan, H.-J. BühringUrine as a Source of Stem Cells, by Christina Benda, Ting Zhou, Xianming Wang, Weihua Tian, Johannes Grillari, Hung-Fat Tse, Regina Grillari-Voglauer, Duanqing Pei, Miguel A. Esteban Expansion of Mesenchymal Stem/Stromal Cells under Xenogenic-Free Culture Conditions, by Sven Kinzebach, Karen Bieback Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications, by Danielle Minteer, Kacey G Marra, J Peter Rubin Potential for Osteogenic and Chondrogenic Differentiation of MSC, by Antonina Lavrentieva, Tim Hatlapatka, Anne Neumann, Birgit Weyand, Cornelia Kasper Potential for Neural Differentiation of Mesenchymal Stem Cells, by Letizia Ferroni, Chiara Gardin, Ilaria Tocco, Roberta Epis, Alessandro Casadei, Vincenzo Vindigni, Giuseppe Mucci, Barbara Zavan Migratory Properties of Mesenchymal Stem Cells, by Thomas Dittmar, Frank EntschladenDissecting Paracrine Effectors for Mesenchymal Stem Cells, by Stefania Bruno, Federica Collino, Ciro Tetta, Giovanni Camussi Proteomics Approaches in the Identification of Molecular Signatures of Mesenchymal Stem Cells, by Yin Xiao, Jiezhong ChenDoes the Adult Stroma Contain Stem Cells?, by Richard Schäfer

The Cell-Surface Interaction, by J. S. Hayes, E. M. Czekanska and R. G. Richards. Studying Cell-Surface Interactions In Vitro: A Survey of Experimental Approaches and Techniques, by Stefanie Michaelis, Rudolf Robelek and Joachim Wegener. Harnessing Cell-Biomaterial Interactions for Osteochondral Tissue Regeneration, by Kyobum Kim, Diana M. Yoon, Antonios G. Mikos and F. Kurtis Kasper. Interaction of Cells with Decellularized Biological Materials, by Mathias Wilhelmi, Bettina Giere and Michael Harder. Evaluation of Biocompatibility Using In Vitro Methods: Interpretation and Limitations, by Arie Bruinink and Reto Luginbuehl. Artificial Scaffolds and Mesenchymal Stem Cells for Hard Tissues, by Margit Schulze and Edda Tobiasch. Bioactive Glass-Based Scaffolds for Bone Tissue Engineering, by Julia Will, Lutz-Christian Gerhardt and Aldo R. Boccaccini. Microenvironment Design for Stem Cell Fate Determination, by Tali Re’em and Smadar Cohen. Stem Cell Differentiation Depending on Different Surfaces, by Sonja Kress, Anne Neumann, Birgit Weyand and Cornelia Kasper. Designing the Biocompatibility of Biohybrids, by Frank Witte, Ivonne Bartsch and Elmar Willbold. Interaction of Cartilage and Ceramic Matrix, by K. Wiegandt, C. Goepfert, R. Pörtner and R. Janssen. Bioresorption and Degradation of Biomaterials, by Debarun Das, Ziyang Zhang, Thomas Winkler, Meenakshi Mour, Christina I. Günter, Michael M. Morlock, Hans-Günther Machens and Arndt F. Schilling.

Engineered MSCs from Patient-Specific iPS Cells, by Irina Eberle, Mohsen Moslem, Reinhard Henschler, Tobias Cantz Fate of Intravenously Injected Mesenchymal Stem Cells and Significance for Clinical Application, by Beate Wagner, Reinhard Henschler The Implications of Stem Cell Applications for Diseases of the Respiratory System, by Mei Ling Lim, Philipp Jungebluth, Paolo Macchiarini Potential of Mesenchymal Stem Cell Applications in Plastic and Reconstructive Surgery, by Birgit Weyand, Peter M. Vogt General Principles for the Regeneration of Bone and Cartilage, by Michael Jagodzinski, C. Haasper Adult Mesenchymal Stem Cells Explored in the Dental Field, by K. M. Fawzy El-Sayed, C. Dörfer, F. Fändrich, F. Gieseler, M. H. Moustafa, H. Ungefroren Mesenchymal Stem Cell Therapy and Lung Diseases, by Khondoker M. Akram, Sohel Samad, Monica Spiteri, Nicholas R. Forsyth Mesenchymal Stem Cells as Cellular Immunotherapeutics in Allogeneic Hematopoietic Stem Cell Transplantation, by Claudia Papewalis, Daniela Topolar, Barbara Götz, Stefan Schönberger, Dagmar Dilloo New Cell-Based Therapy Paradigm: Induction of Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells into Pro-Inflammatory MSC1 and Anti-inflammatory MSC2 Phenotypes, by Aline M. Betancourt Interactions Between Mesenchymal Stem Cells and Dendritic Cells, by Grazia Maria Spaggiari, Lorenzo Moretta MSC and Tumors: Homing, Differentiation, and Secretion Influence Therapeutic Potential, by Naomi D’souza, Jorge Sans Burns, Giulia Grisendi, Olivia Candini, Elena Veronesi, Serena Piccinno, Edwin M. Horwitz, Paolo Paolucci, Pierfranco Conte, Massimo Dominici Sources of Mesenchymal Stem Cells: Current and Future Clinical Use, by Michela Pozzobon, Martina Piccoli, Paolo De Coppi Role of the EU Framework in Regulation of Stem Cell-Based Products, by Giovanni Migliaccio, Cristina Pintus