Stem Cell-Based Tissue Repair

405 Pages·2010·5.745 MB·English

by  Raphael Gorodetsky, Richard Schäfer;

Edited by Raphael Gorodetsky and Richard Schäfer
Stem Cell-Based Tissue Repair
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Stem Cell-Based Tissue Repair

Stem Cell-Based Tissue Repair
Edited by
Raphael Gorodetsky
Sharett Institute of Oncology, Hadassah Hebrew-University, Jerusalem, Israel
Richard Scha¨ fer
Harvard Stem Cell Institute, Harvard University, Cambridge MA, USA
ISBN:978-1-84973-001-3
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rTheRoyalSocietyofChemistry2011
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Preface
Regenerative medicine is a new medical science aimed to overcome the biolo-
gical limitations in the restoration of damaged or missing organs in humans.
In general, severely damaged or amputated organs in mammals would not
regenerate spontaneously, as happens in organisms lower in the phylogenetic
tree. This young field of medical science is still struggling to solve basic bio-
logical barriers and obstacles associated with the limited postnatal tissue
regeneration potential.
Based on the need to design and replace damaged tissues, a new approach
termed ‘‘tissue engineering’’ was conceptualized with the aim of incorporating
and merging material science technologies with transplantation of cellular
biological components. New biodegradable and biocompatible materials have
been designed, attempting to create scaffolds which do not induce toxic,
immunogenic or inflammatory responses. The simpler proposed technologies
were based on implants of the cell-friendly matrices alone. The cells from the
damaged tissuewereexpectedtobeinducedtomigrate,proliferateandfillthe
empty scaffolds to restore the function of the repaired organ.
Nevertheless,theanticipationtoyieldafunctionaltissuejustbyimplantsof
bio-mimetic materials has been too optimistic. It became clear that such bio-
technologiesshouldincorporatethemajorplayersintheregenerativeprocessin
theformofimplantedfunctionalcells.Unfortunately,merelyinjectingisolated
lineage-specific differentiated cells into the failing organs could not induce a
significant repair.
The only routinely used cell based therapy that is applied is bone marrow
transplantation, where progenitors of the hematopoietic system are injected.
But even in such commonly used treatments, the delivered cells need the sup-
port of their specific homing niche in the form of the bone marrow stroma to
survive and regenerate the hematopoietic system.
With the recognition of the cellular component as a critical factor in
regenerative technologies, the introduction of stem cells of different types and
StemCell-BasedTissueRepair
EditedbyRaphaelGorodetskyandRichardScha¨fer
rTheRoyalSocietyofChemistry2011
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
v
vi Preface
origins drewmuchoftheattention inthis field. The fact thatsuchcells canbe
induced to differentiate to a wide spectrum of cell types within the same germ
layer,orinthecaseofveryimmaturecells,totrans-differentiatetoevenawider
range of cells types, seemed to render them the holy grail for regenerative
medicine.Moreover,recentlyitwas proposedthat notonlycelldifferentiation
but also their cross talk with resident cell types of the host and immuno-
modulation may be a major factor in successful stem/progenitor based tissue
regeneration.
The research and accumulated knowledge on stem cells derivation, identifi-
cationandspecificmarkershassoaredinrecentyears.Nevertheless,thegoalof
finding ways to introduce the cells into the organs to regain lost functions has
so far yielded only very limited results. The field still waits for major break-
throughs to get closer to the clinics.
This book aims to present a wide range of approaches on stem cells based
regenerativemedicine.Issuesrelatedtoisolation,derivation,identificationand
differentiationofprogenitorcellsandassemblyofmatricestocarrythecellsare
reviewed. These include know-how on new approaches of targeting and
transporttheadequatecellstotheirdestinationandenabletheirintegrationin
the target damaged organs.
The contributors to this book include experts in a wide range of areas
associated with regenerative medicine. Different points of view and possible
approachesfortissueregeneration,aswellasrelevantconsiderationsofhowto
incorporate the wide range of stem cells sources in different regenerative
treatment regimens are presented. The book also emphasizes the remaining
unsolved issues to be addressed by future research.
The editors wish to express their gratitude to the authors of the different
chapters for their important contribution and for their success to highlight
diverse issues associated with stem cells based regenerative medicine. Though
this book attempts to present an up-to-date overview of this field, considering
its very dynamic nature, the editors would appreciate any comments or sug-
gestions from the readership. Such input could be incorporated in the next
editions.
Raphael Gorodetsky and Richard Schaefer
Contents
Chapter 1 Promisesand Limitations in theApplication of Cell Therapy
for Tissue Regeneration 1
Raphael Gorodetsky
1.1 Factors Affecting Morphogenesis and Normal
Cellular Organization in Tissues and Organs 1
1.2 Endogenous Cell-based Repair of Damaged Tissues 2
1.3 Cellular Implants for Regenerative Therapies of
Damaged Organs and Tissues 3
1.4 Potential Practical Application of Stem Cells for
Tissue Regeneration 4
1.5 Regenerative Medicine 6
1.6 Examples of Tissue Engineering Approaches 8
References 10
Chapter 2 Adult Non-hematopoietic Stem Cells and Progenitor Cells
(aNHSCs) 22
R. Scha¨fer and L. Dahe´ron
2.1 Introduction and General Remarks on the Nature of
aNHSCs 22
2.2 Characterization of aNHSCs 28
References 35
Chapter 3 Screening Approaches for Stem Cells 45
David G. Buschke, Derek J. Hei, Kevin W. Eliceiri and
Brenda M. Ogle
3.1 Dynamics of Stem Cells 45
3.2 Characterization is Critical 48
StemCell-BasedTissueRepair
EditedbyRaphaelGorodetskyandRichardScha¨fer
rTheRoyalSocietyofChemistry2011
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viii Contents
3.3 What is Stem Cell Screening? 51
3.4 Stem Cell Screening 52
3.5 Summary 68
References 69
Chapter 4 Hematopoietic Stem Cells and their Role in Regenerative
Medicine 81
Eitan Fibach
4.1 The Human Hematopoietic Stem Cell 81
4.2 Clinical Uses of HSC 82
4.3 Ex Vivo Expansion of HSC 84
4.4 Expanding HSC in Cytokine Cocktails 84
4.5 Expansion of HSC by Coculturing with Stroma
Feeder Cells 85
References 86
Chapter5 CordandCordBlood:ValuableResourceswithPotentialfor
Liver Therapy 89
Saba Habibollah, Marcin Jurga, Nico Forraz and Colin
McGuckin
5.1 Introduction 89
5.2 The Liver—A Unique Organ 90
5.3 Current Management of Liver Disorders 92
5.4 Stem Cell-based Therapy—An Alternative Approach
in Healthcare 93
5.5 Pluripotent Stem Cells Derived from Cord and Cord
Blood 95
5.6 HepaticDifferentiationPropertiesofAdultStemCells 96
5.7 Can Cord and Cord Blood Stem Cells Regenerate
Liver Tissue? 97
5.8 Molecular Mechanisms and Stem Cell Culture Proto-
cols for Liver Differentiation 99
5.9 Liver Tissue Engineering 102
5.10 Clinical Trials 103
List of Abbreviations 105
References 105
Chapter 6 Induced Pluripotent Stem Cells: Their Role in Modeling
Disease and Regenerative Medicine 117
Yonatan Stelzer and Marjorie Pick
6.1 Introduction 117
6.2 Applications for the Reprogramming of Mammalian
Cells 121
Contents ix
6.3 Reducing the Risks Associated with the Use of iPS
Cells 131
6.4 Conclusions 135
References 136
Chapter 7 Mesenchymal Stromal/Stem Cells from Tissue Repair to
Destruction of Tumor Cells 141
Rita Bussolari, Giulia Grisendi, Luigi Cafarelli,
Pietro Loschi, Laura Scarabelli, Antonio Frassoldati,
Michela Maur, Giorgio De Santis, Paolo Paolucci,
Pierfranco Conte and Massimo Dominici
7.1 Stromal Cells and Tumor 141
7.2 RoleofMesenchymalStromal/StemCellsinaTumor
Microenvironment 143
7.3 MSCs and Tumors: Between Growth and Inhibition 146
7.4 Mesenchymal Stromal/Stem Cells as Vehicles for
Cancer Therapy 148
7.5 Mesenchymal Stromal/Stem Cells can Efficiently
Delivery Death Ligands 152
References 153
Chapter 8 Fibrin-based Matrices to Support Stem Cell-Based Tissue
Regeneration 159
Raphael Gorodetsky, Iris Mironi-Harpaz and Dror Seliktar
8.1 Background: The Pitfalls of Matrix-based
Three-dimensional Tissue Engineering 159
8.2 Fibrin Structure, its Formation and Mechanism of
Action in Damaged Tissue 160
8.3 Proposed Mechanisms for Cell Interactions with
Fibrin(ogen) 161
8.4 Utilization of Products Derived from Fibrinogen and
Thrombin Purified from Blood Plasma 162
8.5 Tissue Engineering with Modified Fibrin Matrices 162
8.6 Conclusions 168
References 168
Chapter 9 Culturing Non-hematopoietic Mesenchymal Stromal Cells
and Requirements of GMP in Stem Cell-based Therapies 178
Karen Bieback, Marianna Karagianni, Gerlinde Schmidtke-
Schrezenmeier, Natalie Fekete and Hubert Schrezenmeier
9.1 Introduction 178
9.2 What Are MSC? 179