CONTENTS -- Contributors -- Preface -- Part I Stem Cells and Effects of Microenvironment -- Chapter 1 MicroEngineering the Embryonic Stem Cell Environment Yu-Shik Hwang, Bong Geun Chung, Alice Mira Chung and Ali Khademhosseini -- 1. Embryonic Stem Cells and Tissue Engineering -- 1.1 Embryonic stem cells -- 1.2 Tissue engineering -- 2. Microenvironment -- 2.1 Cell-cell contact -- 2.2 Cell - ECM -- 2.3 Cell-soluble factor interactions -- 3. Microengineering to Control ESC Microenvironment -- 3.1 Microfluidic platforms for controlling cell-soluble factor interactions -- 3.2 Surface micropatterning for controlling cell-cell contacts -- 3.3 High-throughput microarray for screening microenvironments -- 3.4 3D scaffolds for culturing stem cells -- 4. Conclusions -- Acknowledgments -- References -- Chapter 2 Stem Cells Therapy for Ischemic Cardiovascular Diseases: New Insights on Mechanisms and Fate of the Implanted Cells Nicolas Noiseux, Jean-François Cailhier and Samer Mansour -- 1. Background: Ischemic Cardiovascular Diseases -- 2. Myocardial Infarct: Pathophysiology -- 3. Stem Cells for Myocardial Repair -- 4. What is the Best Donor Cell Source for Cellular Therapy? -- 4.1 Hematopoietic stem cells (HSC) and endothelial progenitor stem cells (EPC) -- 4.2 Bone marrow-derived mesenchymal stem cells (MSC) -- 4.3 Skeletal myoblasts -- 4.4 Cardiac resident stem cells -- 5. Suspected Mechanisms of Stem Cell Repair -- 5.1 Cardiac regeneration by cell therapy and evidence for transdifferentiation -- 5.2 Cellular fusion -- 5.3 Indirect and paracrine effects -- 5.4 Inflammation and neovascularization -- 6. Delivery and Homing of Stem Cells -- 7. Optimizing the Reparative Biology of Stem Cells -- 8. Examples of Stem Cells Clinical Applications in Acute MI -- 8.1 Unselected bone marrow cells.

8.2 Selected bone marrow cell populations: Are they the optimal stem cell source? -- 8.3 The use of CD133 stem cells for acute and chronic ischemic cardiomyopathy -- 8.4 First ongoing clinical Canadian experience in selected bone marrow stem cell therapy: Comparison of intracoronary injection of CD133 bone marrow stem cells to placebo in patients after acute myocardial infarction and left ventricular dysfunction: COMPARE-AMI trial -- 9. Conclusion -- References -- Chapter 3 The Role of Mechanical Forces in the Cardiomyogenic Differentiation of Stem Cells Daniel Pelaez, Joshua M. Hare and Herman S. Cheung -- 1. Introduction -- 1.1 Relevance of biomechanical forces -- 1.2 Mechanical forces and the cardiovascular system -- 1.3 Tissue engineering considerations in myocardial regeneration -- 2. Cell-Based Therapies for Myocardial Regeneration -- 2.1 Skeletal muscle-derived cells -- 2.1.1 Skeletal myoblasts (SMBs) -- 2.1.2 Skeletal muscle stem cells (SkmSC) -- 2.2 Resident cardiac progenitor cells -- 2.2.1 c-Kit cells -- 2.2.2 Isl-1 cells -- 2.3 Stem cells -- 2.3.1 Embryonic stem cells (ESC) -- 2.3.2 Mesenchymal stem cells (MSC's) -- 2.3.3 Other stem cells -- 3. Mechanical Forces and Cardiovascular Differentiation -- 3.1 Frequency -- 3.2 Magnitude of strain -- 3.3 Duration of stimuli application -- 4. Current Models of Mechanotransduction -- 4.1 TGF-β superfamily -- 4.2 Notch signaling -- 4.3 PDGF-BB signaling -- 4.4 Insulin and insulin-like growth factor I (IGF-I) -- 4.5 Reactive oxygen species (ROS) activated pathways -- 5. Conclusions -- References -- Chapter 4 Aging and Stem Cell Therapy: A Review and Highlights of Current Controversies Madhur Nayan, Nina Nouraeyan, Wendy S. Chiu and Dominique Shum-Tim -- 1. Introduction to Stem Cell Senescence -- 2. Current Controversies -- 3. Definitions of Age -- 3.1 Donor age.

3.2 Passage number (laboratory age) -- 4. Differences in Aged Stem Cells -- 4.1 Proliferation and self-renewal -- 4.2 Differentiation -- 4.3 Morphology -- 4.4 Mobilization -- 5. Effects of Laboratory Manipulations -- 6. Effects of the Aged Microenvironment -- 7. From Bench to Bedside: Clinical Implications -- 8. Conclusion -- References -- Chapter 5 Immunological Basis for Allogeneic Mesenchymal Stem Cell Therapy Rony Atoui and Ray C. J. Chiu -- 1. Introduction -- 2. The Proliferating Sources of Stem Cells -- 3. MSCs: Their Unique Immunotolerant Properties -- 3.1 MSCs as hypo-immunogenic cells -- 3.2 MSCs modulate the function of T-cells -- 3.3 Immunosuppressive property of MSCs -- 4. In Vitro Immune Suppression by MSCs -- 5. Immune Modulation of MSCs in Vivo -- 6. Similarities with Tumor Evasion and "Maternal-Fetal Cell Microchimerism" -- 7. Immune Tolerance of Embryonic, Fetal and Other Adult Stem Cells -- 8. The Immune Tolerance After the Differentiation of Stem Cells -- 9. Current Controversies -- 10. Conclusion -- Acknowledgments -- References -- Chapter 6 Modulation of the Tissue Microenvironment to Enhance the Effects of Cell Transplantation Paul S. Lee and Terrence M. Yau -- 1. Introduction -- 2. Paracrine Mechanisms -- 2.1 Angiogenesis -- 2.2 Mobilization of circulating and bone marrow-derived stem cells -- 2.3 Activation and mobilization of cardiac-resident stem cells -- 2.4 Stabilization of the extracellular matrix -- 3. Enhancing the Paracrine Effects of Cell Transplantation -- 3.1 Altering the microenvironment by modification of donor cells -- 3.1.1 Cell-based gene therapy -- 3.1.1a Angiogenesis -- 3.1.1b Enhanced cell survival -- 3.1.1c Augmentation of endogenous repair mechanisms -- 3.1.1d ECM remodeling -- 3.1.2 Cellular preconditioning -- 3.1.2a Hypoxic and hyperthermic preconditioning -- 3.1.2b Pharmacological preconditioning.

3.2 Altering the microenvironment by pretreatment of the myocardium -- 3.2.1 Pharmacological pretreatment -- 3.2.2 Gene therapy -- 3.2.3 Protein therapy -- 3.2.4 Transmyocardial revascularization -- 3.3 Tissue engineering and biomaterials/biocomposites -- 4. Conclusion -- References -- Chapter 7 Effect of Nanofibrous Scaffolding on Stem Cell Differentiation and Tissue Formation Laura A. Smith and Peter X. Ma -- 1. Introduction -- 2. Methods of Fabricating Biomimetic Nanofibrous Scaffolding -- 2.1 Electrospinning -- 2.2 Self assembly -- 2.3 Thermally induced phase separation -- 3. Effect of Nanofibrous Scaffolding on Stem Cell Behavior -- 3.1 Attachment and proliferation -- 3.2 Differentiation and tissue formation -- 3.3 Potential mechanisms -- 4. Conclusion -- References -- Part II Tissue Engineering and Bioengineering of Stem Cells -- Chapter 8 Genetic Engineering of Human Embryonic Stem Cells: Focusing on Targeted Modification Katherine M. Ruby and Binhai Zheng -- 1. Introduction -- 2. The Basics of Gene Targeting - Lessons from Mouse ES Cells -- 2.1 Stable transfection -- 2.2 Gene targeting frequency -- 2.2.1 The length of homology arms -- 2.2.2 The use of isogenic DNA to generate the homology arms -- 2.2.3 Negative selection -- 2.2.4 Promoterless gene trap targeting strategy -- 2.3 Molecular screens -- 2.4 Reporter genes -- 2.5 Site-specific recombination -- 2.6 Conditional gene targeting -- 3. Targeted Modifications in Human ES Cells -- 3.1 Targeting HPRT - a test locus in male human ES cells -- 3.2 Promoterless gene trap targeting -- 3.3 Targeting a gene not expressed in human ES cells -- 3.4 Viral vector-based gene targeting -- 3.5 Zinc finger nuclease to enhance gene targeting frequency -- 4. Concluding Remarks -- Notes added in proof -- Acknowledgments -- Nomenclature -- References.

Chapter 9 Bio-Artificial Myocardium for the Treatment of Ischemic Heart Disease: First Clinical Experience Juan C. Chachques -- 1. Introduction -- 2. Heart Failure -- 3. From Latissimus Dorsi to Cellular Cardiomyoplasty -- 4. Cell-Based Regenerative Therapy -- 4.1 Limitations of cell therapy -- 5. Stem Cells: New Developments -- 6. Tissue Engineering: State of the Art -- 7. Development of Bio-Artificial Myocardium -- 7.1 Pre-clinical studies -- 7.1.1 Collagen matrix preparation -- 7.1.2 Results -- 7.2 MAGNUM clinical trial -- 7.3 Conclusions of the MAGNUM trial -- 8. New Developments -- 8.1 Elastomeric scaffolds and membranes -- 8.2 Nanomaterials gels -- 8.3 Effect of mechanical stimuli on stem cells -- 8.4 Cardiac pacing and myogenic cell transplantation: the dynamic duo -- 8.4.1 In-vitro cell electrostimulation -- 8.4.2 In-vivo cell electrostimulation -- 9. Conclusions and Perspectives -- 10. Translational Research -- Acknowledgments -- References -- Chapter 10 Stem Cell Bioengineering and Microencapsulation: Current Perspective and Future Potentials Arghya Paul, Jasmine Bhathena and Satya Prakash -- 1. Introduction -- 2. Currently Available Modes of Stem Cell Administration: Potential and Limitations -- 3. Traditional Cell Immobilization Techniques: Potential in Stem Cell Delivery -- 4. Introduction to Artificial Cell: A Promising Stem Cell Delivery System -- 4.1 Designing of artificial cells for use in stem cell therapy -- 4.2 Methods for preparation of artificial cells for stem cell bioengineering applications -- 5. Potential and Current Progress of Artificial Cells in Stem Cell Therapy -- 6. Conclusion and Future Works -- Acknowledgments -- References -- Part III Applications of Cell Therapy - From Bench to Bedside -- Chapter 11 Fetal-Source Stem Cells Pai-Jiun Ho, B. Linju Yen and Men-Luh Yen -- 1. Stem Cells: Definition and Overview.

2. Progenitor/Stem Cells from Fetal Sources.