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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 cell￾based 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

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