Bioreactors for Stem Cell Expansion and Differentiation

357 Pages·2019·14.123 MB·English

by  Cabral, Joaquim S., Silva, Cláudia Lobato da

Bioreactors for Stem
Cell Expansion and
Differentiation
Gene and Cell Therapy Series
Series Editors
Anthony Atala & Graça Almeida-Porada
Published Titles
Placenta: The Tree of Life
edited by Ornella Parolini
Cellular Therapy for Neurological Injury
edited by Charles S. Cox, Jr
Regenerative Medicine Technology: On-a-Chip Applications for Disease
Modeling, Drug Discovery and Personalized Medicine
edited by Sean V. Murphy and Anthony Atala
Therapeutic Applications of Adenoviruses
edited by Philip Ng and Nicola Brunetti-Pierri
Gene and Cell Delivery for Invertebral Disk Degeneration
edited by Raquel Madeira Gonçalves and Mario Adolfo Barbosa
Bioreactors for Stem Cell Expansion and Differentiation
edited by Joaquim M. S. Cabral and Cláudia Lobato da Silva
For more information about this series, please visit:
https://www.crcpress.com/Gene-and-Cell-Therapy/book-series/
CRCGENCELTHE
Gene and Cell Therapy Series
Bioreactors for Stem
Series Editors
Anthony Atala & Graça Almeida-Porada
Cell Expansion and
Published Titles
Placenta: The Tree of Life Differentiation
edited by Ornella Parolini
Cellular Therapy for Neurological Injury
edited by Charles S. Cox, Jr
Regenerative Medicine Technology: On-a-Chip Applications for Disease
Modeling, Drug Discovery and Personalized Medicine
edited by Sean V. Murphy and Anthony Atala
Therapeutic Applications of Adenoviruses
edited by Philip Ng and Nicola Brunetti-Pierri
Gene and Cell Delivery for Invertebral Disk Degeneration
edited by Raquel Madeira Gonçalves and Mario Adolfo Barbosa
Bioreactors for Stem Cell Expansion and Differentiation Edited by
edited by Joaquim M. S. Cabral and Cláudia Lobato da Silva
Joaquim M. S. Cabral
Instituto Superior Técnico, Universidade de
Lisboa,  Lisboa, Portugal
For more information about this series, please visit:
https://www.crcpress.com/Gene-and-Cell-Therapy/book-series/ Cláudia Lobato da Silva
CRCGENCELTHE
Instituto Superior Técnico, Universidade de
Lisboa,  Lisboa, Portugal
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2019 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Printed on acid-free paper
International Standard Book Number-13: 978-1-4987-9590-6 (Hardback)
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts
have been made to publish reliable data and information, but the author and publisher cannot assume
responsibility for the validity of all materials or the consequences of their use. The authors and publishers
have attempted to trace the copyright holders of all material reproduced in this publication and apologize to
copyright holders if permission to publish in this form has not been obtained. If any copyright material has
not been acknowledged please write and let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmit-
ted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented,
including photocopying, microfilming, and recording, or in any information storage or retrieval system,
without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.
com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood
Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and
registration for a variety of users. For organizations that have been granted a photocopy license by the CCC,
a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used
only for identification and explanation without intent to infringe.
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
Contents
Series Preface ...........................................................................................................vii
Preface.......................................................................................................................ix
About the Editors ...................................................................................................xiii
Contributors .............................................................................................................xv
Chapter 1 Large-Scale Culture of 3D Aggregates of Human Pluripotent
Stem Cells.............................................................................................1
Elena F. Jacobson and Emmanuel S. Tzanakakis
Chapter 2 Bioreactors for Human Pluripotent Stem Cell Expansion and
Differentiation ....................................................................................25
Carlos A.V. Rodrigues, Mariana Branco, Diogo E.S. Nogueira,
CRC Press
Teresa P. Silva, Ana Rita Gomes, Maria Margarida Diogo, and
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300 Joaquim M. S. Cabral
Boca Raton, FL 33487-2742
© 2019 by Taylor & Francis Group, LLC
Chapter 3 Differentiation of Human Pluripotent Stem Cells for Red Blood
CRC Press is an imprint of Taylor & Francis Group, an Informa business
Cell Production ...................................................................................47
No claim to original U.S. Government works
Mark C. Allenby, Susana Brito dos Santos, Nicki Panoskaltsis,
Printed on acid-free paper and Athanasios Mantalaris
International Standard Book Number-13: 978-1-4987-9590-6 (Hardback)
Chapter 4 3D Strategies for Expansion of Human Cardiac Stem/Progenitor
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts
have been made to publish reliable data and information, but the author and publisher cannot assume Cells ....................................................................................................63
responsibility for the validity of all materials or the consequences of their use. The authors and publishers
have attempted to trace the copyright holders of all material reproduced in this publication and apologize to Maria João Sebastião, Bernardo Abecasis,
copyright holders if permission to publish in this form has not been obtained. If any copyright material has Manuel J.T. Carrondo, Paula M. Alves, Patrícia Gomes-Alves,
not been acknowledged please write and let us know so we may rectify in any future reprint.
and Margarida Serra
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmit-
ted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented,
including photocopying, microfilming, and recording, or in any information storage or retrieval system, Chapter 5 Bioreactor Protocols for the Expansion and Differentiation of
without written permission from the publishers. Human Neural Precursor Cells in Targeting the Treatment of
Neurodegenerative Disorders .............................................................97
For permission to photocopy or use material electronically from this work, please access www.copyright.
com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood
Arindom Sen, Behnam A. Baghbaderani, Michael S. Kallos,
Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and
registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, Ivar Mendez, and Leo A. Behie
a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used
only for identification and explanation without intent to infringe.
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
v
vi Contents
Chapter 6 Bioprocessing of Human Stem Cells for Therapeutic Use
through Single-Use Bioreactors .......................................................135
Aletta C. Schnitzler, Mark Lalli, Manjula Aysola, Janmeet
Anant, and Julie Murrell
Chapter 7 Bioreactors for the Cultivation of Hematopoietic Stem and
Progenitor Cells ................................................................................165
Marta H.G. Costa, Frederico Castelo Ferreira,
Joaquim M. S. Cabral, and Cláudia Lobato da Silva
Chapter 8 Quality Manufacturing of Mesenchymal Stem/Stromal Cells
Using Scalable and Controllable Bioreactor Platforms ....................201
Sunghoon Jung, Krishna M. Panchalingam, Brian Lee, and
Leo A. Behie
Chapter 9 Bioreactor Sensing and Monitoring for Cell Therapy
Manufacturing ..................................................................................243
Ioannis Papantoniou, Toon Lambrechts, Priyanka Gupta,
Sébastien de Bournonville, Niki Loverdou, Liesbet Geris, and
Jean-Marie Aerts
Chapter 10 Bioreactors for Tendon Tissue Engineering: Challenging
Mechanical Demands Towards Tendon Regeneration .....................269
Ana I. Gonçalves, Dominika Berdecka, Márcia T. Rodrigues,
Rui L. Reis, and Manuela E. Gomes
Chapter 11 Liver Tissue Engineering .................................................................301
Sara Morini, Natalia Sánchez-Romero, Iris Plá Palacín,
Pilar Sainz Arnal, Manuel Almeida, Laurens Verscheijden,
Joana I. Almeida, Alberto Lue, Sara Llorente,
Helen Almeida, Pablo Royo Dachary, Agustín García Gil,
Trinidad Serrano-Aulló, and Pedro M. Baptista
Index ......................................................................................................................329
Series Preface
Gene and cell therapies have evolved in the past several decades from a conceptual
promise to a new paradigm of therapeutics, able to provide effective treatments for
a broad range of diseases and disorders that previously had no possibility of cure.
The fast pace of advances in the cutting-edge science of gene and cell therapy, and
supporting disciplines ranging from basic research discoveries to clinical applica-
tions, requires an in-depth coverage of information in a timely fashion. Each book in
this series is designed to provide the reader with the latest scientific developments in
the specialized fields of gene and cell therapy, delivered directly from experts who
are pushing forward the boundaries of science.
In this volume of the Gene and Cell Therapy book series, Bioreactors for Stem
Cell Expansion and Differentiation, the editors have assembled a remarkable team of
outstanding investigators and clinicians, who are experts in stem cell biology, 2D and
3D stem cell culture, large-scale expansion, designer bioreactors and microcarriers,
sensing, monitoring, and modeling. The chapters provide cutting-edge information
on next-generation systems used for expansion and/or differentiation of stem cells
from different sources, at a production scale able to meet the needs of the fields of
regenerative medicine and high-throughput screening. In addition, the authors offer
novel insights into bioreactor-based culture systems specific for tissue engineering,
and discuss sophisticated and cost-effective manufacturing strategies that are able
to comply with good manufacturing practices, geared to overcoming technological
shortcomings that currently preclude advancing towards product commercialization.
This book brings together a team of outstanding investigators presenting thought-
provoking articles in the aforementioned fields, and provides a breadth of knowledge
across disciplines, giving the reader a full understanding of the state-of-art and a
sneak preview into the future of these fields.
We would like to thank the volume editors, Cláudia Lobato da Silva and Joaquim
M. S. Cabral, and the authors, all of whom are remarkable experts, for their valu-
able contributions. We would also like to thank our senior acquisitions editor,
C.R. Crumly, and the CRC Press staff for all their efforts and dedication to the Gene
and Cell Therapy book series.
Anthony Atala
Wake Forest Institute for Regenerative Medicine
and
Graça Almeida-Porada
Wake Forest Institute for Regenerative Medicine
vii

Preface
Stem cells have the capacity to self-renew (e.g., make copies of themselves) and
to differentiate into multiple specialized cell types, being an attractive cell source
for cellular therapies, tissue engineering, and toxicological studies. The successful
implementation of stem cell-based therapies and tissue engineering approaches will
require the reproducible production of well-characterized and functional cells or tis-
sues under highly controlled culture conditions.
Stem cell cultivation has been performed, at a research level, in traditional culture
flasks under static conditions, which are limited in terms of cell productivity, their
non-homogeneous nature resulting in concentration gradients (pH, oxygen, nutrients,
metabolites), difficulty of monitoring and control, and extensive handling is required
for feeding/harvesting procedures.
Bioreactors have been successfully employed in the traditional pharmaceutical
industry for decades, allowing a robust and cost-effective production of a wide range
of drugs, and can represent a suitable alternative to overcome the limitations of static
systems for stem cell cultivation. In addition, the knowledge in bioprocessing science
gathered from these fully characterized pharmaceutical processes has the potential
to be translated into the challenging specifications of stem cell culture. Indeed, the
design of bioreactors targeting the expansion (i.e., proliferation under an undifferenti-
ated state) of stem cells or their differentiation into a specific cell/tissue must take into
consideration the challenging specificities of stem cell cultivation, namely: (1) the com-
plexity of non-homogeneous stem cell populations; (2) the occurrence of multiple cell-
to-cell and matrix-to-cell interactions; (3) the suspension/adherent nature of the cells;
and (4) the market approach (autologous (patient-specific) versus allogeneic (donor-
based)), and the ability to comply to Good Manufacturing Practices (GMP), featur-
ing an integrated quality assurance system in order to obtain the authorization from
regulatory agencies towards the production of a safe and efficient medicinal product.
Different types of bioreactors have been developed for stem cell culture, which
will be depicted in this volume of the Cell and Gene Therapy book series entitled
Bioreactors for Stem Cell Expansion and Differentiation.
Chapter 1 by Elena F. Jacobson and Emmanuel S. Tzanakakis, covers the aspects
relevant to the cultivation of human pluripotent stem cells (PSCs) as aggregates,
depicting the requirements of human PSC pluripotency and genomic stability, vari-
ous bioreactor designs for three-dimensional (3D) stem cell cultivation, different cul-
ture media, and feeding strategies. Carlos A.V. Rodrigues and co-workers provide, in
Chapter 2, a review on the developments in human PSC culture in bioreactor-based
systems, particularly focusing on 3D cell culture and bioreactor configurations and
the critical parameters for a successful and efficient expansion and differentiation of
human PSC into cells of the three germ layers, including the generation of organoids.
Chapter 3, written by Mark C. Allenby and colleagues, summarizes the state of the
art of ex vivo methodologies and culture systems for the manufacturing of erythroid
cells from human PSC (including embryonic stem cells (ESCs) and induced pluripo-
tent stem cells (iPSCs)), discussing some of the issues to be addressed to facilitate
ix