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NEW ADVANCES IN STEM
CELL TRANSPLANTATION
Edited by Taner Demirer
New Advances in Stem Cell Transplantation
Edited by Taner Demirer
Published by InTech
Janeza Trdine 9, 51000 Rijeka, Croatia
Copyright © 2012 InTech
All chapters are Open Access distributed under the Creative Commons Attribution 3.0
license, which allows users to download, copy and build upon published articles even for
commercial purposes, as long as the author and publisher are properly credited, which
ensures maximum dissemination and a wider impact of our publications. After this work
has been published by InTech, authors have the right to republish it, in whole or part, in
any publication of which they are the author, and to make other personal use of the
work. Any republication, referencing or personal use of the work must explicitly identify
the original source.
As for readers, this license allows users to download, copy and build upon published
chapters even for commercial purposes, as long as the author and publisher are properly
credited, which ensures maximum dissemination and a wider impact of our publications.
Notice
Statements and opinions expressed in the chapters are these of the individual contributors
and not necessarily those of the editors or publisher. No responsibility is accepted for the
accuracy of information contained in the published chapters. The publisher assumes no
responsibility for any damage or injury to persons or property arising out of the use of any
materials, instructions, methods or ideas contained in the book.
Publishing Process Manager Masa Vidovic
Technical Editor Teodora Smiljanic
Cover Designer InTech Design Team
First published February, 2012
Printed in Croatia
A free online edition of this book is available at www.intechopen.com
Additional hard copies can be obtained from [email protected]
New Advances in Stem Cell Transplantation, Edited by Taner Demirer
p. cm.
ISBN 978-953-51-0013-3
Contents
Preface IX
Part 1 Basic Aspects of Stem Cell Transplantation 1
Chapter 1 Generation of Patient Specific Stem Cells:
A Human Model System 3
Stina Simonsson, Cecilia Borestrom and Julia Asp
Chapter 2 Importance of Non-HLA Gene Polymorphisms in
Hematopoietic Stem Cell Transplantation 25
Jeane Visentainer and Ana Sell
Chapter 3 Relevance of HLA Expression Variants in
Stem Cell Transplantation 39
Britta Eiz-Vesper and Rainer Blasczyk
Chapter 4 The T-Cells’ Role in Antileukemic Reactions -
Perspectives for Future Therapies’ 59
Helga Maria Schmetzer and Christoph Schmid
Chapter 5 Determination of Th1/Th2/Th17 Cytokines in
Patients Undergoing Allogeneic Hematopoietic
Stem Cell Transplantation 83
Adriana Gutiérrez-Hoya, Rubén López-Santiago,
Jorge Vela-Ojeda, Laura Montiel-Cervantes,
Octavio Rodríguez-Cortes and Martha Moreno-Lafont
Chapter 6 Licensed to Kill: Towards Natural Killer
Cell Immunotherapy 103
Diana N. Eissens, Arnold van der Meer and Irma Joosten
Chapter 7 Dendritic Cells in Hematopoietic Stem
Cell Transplantation 127
Yannick Willemen, Khadija Guerti, Herman Goossens,
Zwi Berneman, Viggo Van Tendeloo and Evelien Smits
Chapter 8 Mesenchymal Stem Cells
as Immunomodulators in Transplantation 143
Nadia Zghoul, Mahmoud Aljurf and Said Dermime
VI Contents
Chapter 9 Endovascular Methods for Stem Cell Transplantation 159
Johan Lundberg and Staffan Holmin
Chapter 10 Dynamic Relationships of Collagen Extracellular
Matrices on Cardiac Differentiation of Human
Mesenchymal Stem Cells 183
Pearly Yong, Ling Qian, YingYing Chung and Winston Shim
Part 2 Clinical Aspects of Stem Cell Transplantation 197
Chapter 11 Sources of Hematopoietic Stem Cells 199
Piotr Rzepecki, Sylwia Oborska and Krzysztof Gawroński
Chapter 12 Cryopreservation of Hematopoietic and Non-Hematopoietic
Stem Cells – A Review for the Clinician 231
David Berz and Gerald Colvin
Chapter 13 Hematopoietic Stem Cell Transplantation for
Adult Acute Lymphoblastic Leukaemia 267
Pier Paolo Piccaluga, Stefania Paolini, Francesca Bonifazi,
Giuseppe Bandini, Giuseppe Visani and Sebastian Giebel
Chapter 14 Treatment Options in Myelodysplastic Syndromes 289
Klara Gadó and Gyula Domján
Chapter 15 Mantle Cell Lymphoma:
Decision Making for Transplant 319
Yener Koc and Taner Demirer
Chapter 16 Autologous Peripheral Blood Purified Stem
Cells Transplantation for Treatment of
Systemic Lupus Erythematosus 345
Ledong Sun and Bing Wang
Chapter 17 Allogeneic Hematopoietic Cell Transplantation for
Paroxysmal Nocturnal Hemoglobinuria 355
Markiewicz Miroslaw, Koclega Anna,
Sobczyk-Kruszelnicka Malgorzata, Dzierzak-Mietla Monika,
Zielinska Patrycja, Frankiewicz Andrzej,
Bialas Krzysztof and Kyrcz-Krzemien Slawomira
Chapter 18 Intensified Chemotherapy with Stem Cell Support for
Solid Tumors in Adults: 30 Years of Investigations Can
Provide Some Clear Answers? 371
Paolo Pedrazzoli, Giovanni Rosti, Simona Secondino,
Marco Bregni and Taner Demirer
Chapter 19 Hematopoietic Stem Cell Transplantation
for Malignant Solid Tumors in Children 381
Toshihisa Tsuruta
Contents VII
Chapter 20 Stem Cells in Ophthalmology 405
Sara T. Wester and Jeffrey Goldberg
Chapter 21 Limbal Stem Cell Transplantation and
Corneal Neovascularization 443
Kishore Reddy Katikireddy and Jurkunas V. Ula
Chapter 22 Bone Marrow Stromal Cells for Repair
of the Injured Spinal Cord 471
D. S. Nandoe Tewarie Rishi, Oudega Martin and J. Ritfeld Gaby
Chapter 23 What Do We Know About the Detailed Mechanism on
How Stem Cells Generate Their Mode of Action 495
Peter Riess and Marek Molcanyi
Chapter 24 Autologous Stem Cell Infusion
for Treatment of Pulmonary Disease 505
Neal M. Patel and Charles D. Burger
Chapter 25 Neurologic Sequealae of Hematopoietic Stem
Cell Transplantation (HSCT) 517
Ami J. Shah, Tena Rosser and Fariba Goodarzian
Chapter 26 Adenoviral Infection – Common Complication Following
Hematopoietic Stem Cell Transplantation 533
Iwona Bil-Lula, Marek Ussowicz and Mieczysław Woźniak
Chapter 27 A Systematic Review of Nonpharmacological Exercise-Based
Rehabilitative Interventions in Adults Undergoing Allogeneic
Hematopoietic Stem Cell Transplantation 557
M. Jarden
Preface
This book documents the increased number of stem cell-related research, clinical
applications, and views for the future. The book covers a wide range of issues in cellbased therapy and regenerative medicine, and includes clinical and preclinical
chapters from the respected authors involved with stem cell studies and research from
around the world. It complements and extends the basics of stem cell physiology,
hematopoietic stem cells, issues related to clinical problems, tissue typing,
cryopreservation, dendritic cells, mesenchymal cells, neuroscience, endovascular cells
and other tissues. In addition, tissue engineering that employs novel methods with
stem cells is explored. Clearly, the continued use of biomedical engineering will
depend heavily on stem cells, and this book is well positioned to provide
comprehensive coverage of these developments.
This book will be the the main source for clinical and preclinical publications for
scientists working toward cell transplantation therapies with the goal of replacing
diseased cells with donor cells of various organs, and transplanting those cells close to
the injured or diseased target. With the increased number of publications related to
stem cells and Cell Transplantation, we feel it is important to take this opportunity to
share these new developments and innovations describing stem cell research in the
cell transplantation field with our worldwide readers.
Stem cells have a unique ability. They are able to self renew with no limit, allowing
them to replenish themselves, as well as other cells. Another ability of stem cells is
that they are able to differentiate to any cell type. A stem cell does not differentiate
directly to a specialized cell however- there are often multiple intermediate stages. A
stem cell will first differentiate to a progenitor cell. A progenitor cell is similar to a
stem cell, although they are limited in the number of times they can replicate, and
they are also restricted in which cells they can further differentiate to. Serving as a
sort of repair system for the body, they can theoretically divide without limit in order
to replenish other cells for the rest of the person or animal's natural life. When a stem
cell divides, each new cell has the potential to either remain a stem cell, or become
another type of cell with a more specialized function, such as a muscle cell, a red blood
cell, or a brain cell.
Because of the unique abilities of stem cells, as opposed to a typical somatic cell, they
are currently the target of ongoing research. Research on stem cells is advancing in the
X Preface
knowledge about how an organism develops from a single cell and how healthy cells
replace damaged cells in adult organisms. This promising area of science is also
leading scientists to investigate the possibility of cell-based therapies to treat disease
such as diabetes or heart disease. It is often referred to as regenerative medicine or
reparative medicine.
During this last decade, the number of published articles or books investigating the
role of stem cells in cell transplantation or regenerative medicine increased remarkably
across all sections of the stem cell related journals. The largest number of stem cell
articles was published mainly in the field of neuroscience, followed by the bone,
muscle, cartilage, and hepatocytes. Interestingly, in recent years, the number of stem
cell articles describing the potential use of stem cell therapy and islet transplantation
in diabetes is also slowly increasing, even though this field of endeavor could have
one of the greatest clinical and societal impacts.
Stem cells could have the potential to diminish the problem of the availability of
transplantable organs that, today, limits the number of successful large-scale organ
replacements. Several different methods using stem cells are currently used, but there
are still several obstacles that need to be resolved before attempting to use stem cells in
the clinic. Regarding the transplantation of differentiated cells derived from stem cells,
one can argue that there are several regulatory, scientific, and technical issues, such as
cell manufacturing procedures, regulatory mechanisms for differentiation, and
developing screening methods to avoid developing inappropriate differentiated cells.
One of the next steps in stem cell therapy is the development of treatments that will
function not only at an early stage of transplantation, but will also remain intact
throughout the life of the host recipient.
It will be exciting and interesting for our readers to follow the recent developments in
the field of stem cells and cell transplantation, via this book, such as authors’ search
for the clues to what pathways are used by stem cells to repair tissue, or what can
trigger wound healing, bone growth, and brain repair. Although we are close to
finding pathways for stem cell therapies in many medical conditions, scientists need to
be careful how they use stem cells ethically, and should not rush into clinical trials
without carefully investigating the side effects. Focus must be on Good Manufacturing
Procedures (GMP) and careful monitoring of the long-term effects of transplanted
stem cells in the host.
In conclusion, Cell Transplantation is bridging cell transplantation research in a
multitude of disease models as methods and technology continue to be refined. The
use of stem cells in many therapeutic areas will bring hope to many patients awaiting
replacement of malfunctioning organs, or repairing of damaged tissues. We hope that
this book will be an important tool and reference guide for all scientists worldwide
who work in the field of stem cells and cell transplantation. Additionally, we hope that
it will shed a light upon many important debatable issues in this field.
Preface XI
I would like to thank all authors who contributed this book with excellent up to date
chapters relaying the recent developments in the field of stem cell transplantation to
our readers. I would like to give special thanks to Masa Vidovic, Publishing Process
Manager, and all InTech workers for their valuable contribution in order to make this
book available.
Taner Demirer, MD, FACP
Professor of Medicine, Hematology/Oncology
Dept. of Hematology
Ankara University Medical School
Ankara
Turkey
Part 1
Basic Aspects of Stem Cell Transplantation
1
Generation of Patient Specific Stem Cells:
A Human Model System
Stina Simonsson, Cecilia Borestrom and Julia Asp
Department of Clinical Chemistry and Transfusion Medicine,
Institute of Biomedicine, University of Gothenburg, Gothenburg
Sweden
1. Introduction
In 2006, Shinya Yamanaka and colleagues reported that only four transcription factors
were needed to reprogram mouse fibroblasts back in development into cells similar to
embryonic stem cells (ESCs). These reprogrammed cells were called induced pluripotent
stem cells (iPSCs). The year after, iPSCs were successfully produced from human
fibroblasts and in 2008 reprogramming cells were chosen as the breakthrough of the year
by Science magazine. In particular, this was due to the establishment of patient-specific
cell lines from patients with various diseases using the induced pluripotent stem cell
(iPSC) technique. IPSCs can be patient specific and therefore may prove useful in several
applications, such as; screens for potential drugs, regenerative medicine, models for
specific human diseases and in models for patient specific diseases. When using iPSCs in
academics, drug development, and industry, it is important to determine whether the
derived cells faithfully capture biological processes and relevant disease phenotypes. This
chapter provides a summary of cell types of human origin that have been transformed
into iPSCs and of different iPSC procedures that exist. Furthermore we discuss
advantages and disadvantages of procedures, potential medical applications and
implications that may arise in the iPSC field.
1.1 Preface
For the last three decades investigation of embryonic stem (ES) cells has resulted in better
understanding of the molecular mechanisms involved in the differentiation process of ES
cells to somatic cells. Under specific in vitro culture conditions, ES cells can proliferate
indefinitely and are able to differentiate into almost all tissue specific cell lineages, if the
appropriate extrinsic and intrinsic stimuli are provided. These properties make ES cells an
attractive source for cell replacement therapy in the treatment of neurodegenerative
diseases, blood disorders and diabetes. Before proceeding to a clinical setting, some
problems still need to be overcome, like tumour formation and immunological rejection of
the transplanted cells. To avoid the latter problem, the generation of induced pluripotent
stem (iPS) cells have exposed the possibility to create patient specific ES-like cells whose
differentiated progeny could be used in an autologous manner. An adult differentiated cell
has been considered very stable, this concept has however been proven wrong
experimentally, during the past decades. One ultimate experimental proof has been cloning