Biomaterials as Stem Cell Niche
Studies in Mechanobiology, Tissue Engineering and Biomaterials
1st Edition
Published on 30. September 2010
VIII, 309 pages
978-3-642-13893-5 (ISBN)
Description
Recent developments in stem cell biology have opened new directions in cell therapy. This book provides the state-of-the-art developments in using biomaterials as artificial niches for engineering stem cells, both for the purpose of better understanding their biology under 3D biomimetic conditions as well as for developing new strategies for efficient long term maintenance and directed differentiation of stem cells into various therapeutic lineages. Animal and human stem cells of both embryonic and adult origin are discussed with applications ranging from nerve regeneration, orthopedics, cardiovascular therapy, blood cell generation and cancer therapy. Both synthetic and natural biomaterials are reviewed with emphasis on how material-stem cell interactions direct specific signaling pathways and ultimately modulate the cell fate. This book is valuable for biomaterial scientists, tissue engineers, clinicians as well as stem cell biologists involved in basic research and applications of adult and embryonic stem cells.
More details
Other editions
Additional editions
Content
1 - Preface [Seite 5]
2 - Contents [Seite 7]
3 - Engineering ECM Complexity into Biomaterials for Directing Cell Fate [Seite 9]
3.1 - Abstract [Seite 9]
3.2 - 1. Cell--ECM Interactions [Seite 9]
3.2.1 - 1.1 ECM Composition and Signaling [Seite 10]
3.2.2 - 1.2 ECM Regulation [Seite 11]
3.2.2.1 - 1.2.1 Proteolytic Processing of the ECM [Seite 11]
3.2.2.2 - 1.2.2 Mechanochemical Translation of Cell-binding ECM Domains [Seite 13]
3.3 - 2. ECM and the Stem Cell Niche [Seite 16]
3.3.1 - 2.1 Integrins: A Sign of ''Stemness'' [Seite 16]
3.3.2 - 2.2 Neural Stem Cells and Integrin/ECM Alterations [Seite 17]
3.3.2.1 - 2.2.1 Integrin and ECM Profile During Neural Development [Seite 17]
3.3.2.2 - 2.2.2 ECM and Integrin Profile in Adult Neural Stem Cell Niche [Seite 18]
3.3.2.3 - 2.2.3 Functional Role of ECM/Integrin Interactions [Seite 19]
3.4 - 3. Current Biomaterials Approaches [Seite 20]
3.4.1 - 3.1 Biomimetic Approaches [Seite 20]
3.4.2 - 3.2 Engineering Protein Variants [Seite 21]
3.4.3 - 3.3 Future Directions for Biomaterials as Stem Cell Niches [Seite 22]
3.5 - References [Seite 23]
4 - Functional Biomaterials for Controlling Stem Cell Differentiation [Seite 27]
4.1 - Abstract [Seite 27]
4.2 - 1. Introduction [Seite 28]
4.2.1 - 1.1 Emergence of Stem Cell Engineering in Regenerative Medicine [Seite 28]
4.2.2 - 1.2 Stem Cell Sources [Seite 28]
4.3 - 2. Stem Cell Expansion and Differentiation Using Biomaterials [Seite 29]
4.3.1 - 2.1 Roles of ECM in Stem Cell Differentiation [Seite 29]
4.3.2 - 2.2 Mimicking ECM with Synthetic Biomaterials [Seite 30]
4.3.2.1 - 2.2.1 Mimicking the Biophysical and Biochemical Properties of ECM [Seite 30]
4.3.2.1.1 - Functionalization of Synthetic Substrates with ECM Derived Ligands [Seite 31]
4.3.2.2 - 2.2.2 Effects of the Cell--Matrix Interface [Seite 31]
4.3.2.2.1 - Surface Chemistry and Interfacial Energy [Seite 31]
4.3.2.3 - 2.2.3 Mineralization of Matrix Materials [Seite 37]
4.3.2.3.1 - Mineralization of Polymeric Matrices [Seite 38]
4.3.2.3.2 - Effect of Mineralization on Cell Adhesion, Proliferation and Differentiation [Seite 38]
4.3.2.4 - 2.2.4 Mechanical Properties [Seite 40]
4.3.3 - 2.3 Biomaterial Based Delivery of Soluble Factors for 3D Cell Culture [Seite 40]
4.3.3.1 - 2.3.1 Incorporation of Bioactive Agents into Matrix Materials [Seite 40]
4.3.3.2 - 2.3.2 Effects of Controlled Delivery of Bioactive Agents on Stem Cell Differentiation [Seite 42]
4.3.3.2.1 - Delivery of Bioactive Agents to Embryonic Stem Cells [Seite 42]
4.3.3.2.2 - Tissue Specific Differentiation of Stem Cells Using Delivery of Bioactive Agents [Seite 44]
4.3.4 - 2.4 In Vivo Applications [Seite 45]
4.3.5 - 2.5 Future Perspectives [Seite 46]
4.4 - Acknowledgments [Seite 47]
4.5 - References [Seite 47]
5 - Integration of Biomaterials into 3D Stem Cell Microenvironments [Seite 53]
5.1 - Abstract [Seite 53]
5.2 - 1. Introduction [Seite 53]
5.2.1 - 1.1 Culture in Two or Three Dimensions [Seite 55]
5.2.2 - 1.2 Strategies for Biomaterial Control of the 3D Microenvironment [Seite 55]
5.3 - 2. Scaffolds [Seite 56]
5.4 - 3. Encapsulation [Seite 59]
5.5 - 4. Microcarriers and Microparticles [Seite 60]
5.5.1 - 4.1 Microcarriers [Seite 61]
5.5.2 - 4.2 Microparticles [Seite 61]
5.6 - 5. Summary and Conclusions [Seite 63]
5.7 - References [Seite 63]
6 - Stem Cell Interaction with Topography [Seite 68]
6.1 - Abstract [Seite 68]
6.2 - 1. Introduction [Seite 68]
6.2.1 - 1.1 Extracellular Topography [Seite 69]
6.2.2 - 1.2 Nanotopography [Seite 70]
6.3 - 2. Nanofabrication Techniques [Seite 71]
6.4 - 3. Stem Cells Reception to Topography [Seite 75]
6.4.1 - 3.1 Embryonic Stem Cells [Seite 75]
6.4.2 - 3.2 Neural Progenitor Cells/Neural Stem Cells [Seite 77]
6.4.3 - 3.3 Mesenchymal Stem Cells [Seite 78]
6.5 - 4. Making Sense of Physical Cues in the Extracellular Matrix: Mechanotransduction [Seite 81]
6.5.1 - 4.1 Introduction to the ECM [Seite 81]
6.5.2 - 4.2 Mechanotransduction: A Direct Connection? [Seite 82]
6.5.3 - 4.3 Connecting with the ECM: Cell--Matrix Interactions [Seite 82]
6.5.4 - 4.4 Integrins and Focal Adhesions: Inside Out and Outside In [Seite 84]
6.5.5 - 4.5 Cytoskeleton: Force Transmission [Seite 85]
6.5.5.1 - 4.5.1 Cell Exerting Forces on the Underlying Substrate [Seite 85]
6.5.6 - 4.6 Filopodia: Probing the ECM [Seite 86]
6.5.7 - 4.7 Nucleus: Gene Regulation [Seite 87]
6.6 - 5. Conclusion [Seite 87]
6.7 - References [Seite 88]
7 - The Nanofiber Matrix as an Artificial Stem Cell Niche [Seite 95]
7.1 - Abstract [Seite 95]
7.2 - 1. The Stem Cell Niche [Seite 95]
7.3 - 2. Nanoscale Topography in the Extracellular Matrix [Seite 97]
7.4 - 3. Methods to Generate Nanofibrous Matrices [Seite 98]
7.4.1 - 3.1 Electrospinning [Seite 98]
7.4.2 - 3.2 Self-assembly [Seite 100]
7.4.3 - 3.3 Solution Phase Separation [Seite 102]
7.4.4 - 3.4 Comparison of Nanofiber Generation Methods [Seite 104]
7.5 - 4. Nanofibrous Matrices for Stem Cell Expansion [Seite 105]
7.5.1 - 4.1 Nanofiber-mediated Expansion of Human Hematopoietic Stem Cells (HSCs) [Seite 105]
7.5.2 - 4.2 Nanofiber-mediated Expansion of Neural Stem Cells (NSCs) [Seite 108]
7.5.3 - 4.3 Nanofiber-mediated Expansion of Embryonic Stem Cells (ESCs) [Seite 108]
7.5.4 - 4.4 Nanofiber-mediated Expansion of Mesenchymal Stem Cells (MSCs) [Seite 109]
7.6 - 5. Nanofiber Matrices for Differentiation of Stem Cells [Seite 109]
7.6.1 - 5.1 Nanofiber-mediated Stem Cell Differentiation into Neuronal Lineages [Seite 110]
7.6.2 - 5.2 Nanofiber-mediated Stem Cell Differentiation into Chondrogenic and Osteogenic Lineages [Seite 112]
7.6.3 - 5.3 Nanofiber-mediated Stem Cell Differentiation into Myogenic Lineage [Seite 114]
7.7 - 6. Nanofibrous Matrices for Stem Cell Delivery [Seite 115]
7.8 - 7. Summary [Seite 117]
7.9 - References [Seite 118]
8 - Micropatterned Hydrogels for Stem Cell Culture [Seite 125]
8.1 - Abstract [Seite 125]
8.2 - 1. Introduction: Application of Biomaterial Technologies to Stem Cell Research [Seite 126]
8.3 - 2. Stem Cells [Seite 128]
8.3.1 - 2.1 MSC General Characteristics [Seite 128]
8.3.2 - 2.2 MSC Differentiation and Plasticity [Seite 129]
8.4 - 3. Hydrogels [Seite 130]
8.4.1 - 3.1 Natural Versus Synthetic Polymers [Seite 131]
8.4.2 - 3.2 Gelation Mechanisms [Seite 131]
8.4.2.1 - 3.2.1 Radical Chain Polymerization [Seite 132]
8.4.2.2 - 3.2.2 Chemical Cross-linking [Seite 132]
8.4.3 - 3.3 Functionalization of Hydrogels [Seite 132]
8.4.3.1 - 3.3.1 Biodegradable Hydrogels [Seite 132]
8.4.3.2 - 3.3.2 Biomimetic hydrogels [Seite 133]
8.5 - 4. Micropatterning [Seite 133]
8.5.1 - 4.1 Microfabrication Technology [Seite 134]
8.5.2 - 4.2 Applications in Hydrogel Patterning [Seite 135]
8.5.2.1 - 4.2.1 Photolithography [Seite 135]
8.5.2.2 - 4.2.2 Laser-scanning lithography [Seite 136]
8.5.2.3 - 4.2.3 Stop-flow Lithography [Seite 137]
8.5.2.4 - 4.2.4 Optofluidic Maskless Lithography [Seite 138]
8.5.2.5 - 4.2.5 Photodegradation [Seite 139]
8.5.2.6 - 4.2.6 Micromolding [Seite 140]
8.5.2.7 - 4.2.7 Two-dimensional Templating [Seite 141]
8.6 - 5. Micropatterning Hydrogels with Embedded Cells [Seite 141]
8.6.1 - 5.1 Culture of One Cell Type [Seite 142]
8.6.1.1 - 5.1.1 Cell Viability [Seite 142]
8.6.1.2 - 5.1.2 Cell Migration (and Morphology) [Seite 143]
8.6.1.3 - 5.1.3 Cell Differentiation [Seite 145]
8.6.2 - 5.2 Culture of Multiple Cell Types [Seite 145]
8.6.2.1 - 5.2.1 Microfluidics [Seite 145]
8.6.2.2 - 5.2.2 Bioreactors [Seite 147]
8.6.2.3 - 5.2.3 Micromolding [Seite 147]
8.6.2.4 - 5.2.4 Stop-flow Lithography [Seite 148]
8.7 - 6.Future Outlook [Seite 148]
8.8 - References [Seite 149]
9 - Microengineering Approach for Directing Embryonic Stem Cell Differentiation [Seite 159]
9.1 - Abstract [Seite 159]
9.2 - 1. Introduction [Seite 159]
9.3 - 2. Control of the Cellular Microenvironment [Seite 161]
9.3.1 - 2.1 Cell--cell Contacts [Seite 161]
9.3.2 - 2.2 Cell--soluble Factor Interactions [Seite 162]
9.3.3 - 2.3 Cell--extracellular Matrix Interactions [Seite 163]
9.4 - 3. Microengineering the Environment [Seite 164]
9.4.1 - 3.1 Microfluidic Platforms for Controlling Cell--soluble Factor Interactions [Seite 165]
9.4.2 - 3.2 Controlled Microbioreactors [Seite 166]
9.4.3 - 3.3 Surface Micropatterning for Controlling Cell--cell Contacts [Seite 167]
9.4.4 - 3.4 High-throughput Microarrays for Screening Microenvironments [Seite 169]
9.4.5 - 3.5 Three Dimensional Scaffolds for Culturing ESCs [Seite 170]
9.4.6 - 3.6 Tissue Engineering Using Assembly of Microengineered Building Blocks [Seite 170]
9.5 - 4. Conclusions [Seite 172]
9.6 - References [Seite 173]
10 - Biomaterials as Stem Cell Niche: Cardiovascular Stem Cells [Seite 178]
10.1 - Abstract [Seite 178]
10.2 - 1. Introduction [Seite 179]
10.3 - 2. Adult Cardiovascular Stem Cells and Their Niches [Seite 179]
10.3.1 - 2.1 Cardiac Stem Cells [Seite 179]
10.3.2 - 2.2 Endothelial Progenitor Cells [Seite 181]
10.3.3 - 2.3 Mural Cell Progenitors/Mesenchymal Stem Cells [Seite 182]
10.3.4 - 2.4 Adult Cardiovascular Stem Cell Niches [Seite 183]
10.4 - 3. Biomaterials as Stem Cell Niches for 3D Cell Culture [Seite 184]
10.4.1 - 3.1 3D Cell Culture Systems for Pluripotent Stem Cells [Seite 184]
10.4.2 - 3.2 3D Cell Culture Systems for Adult Stem Cells [Seite 187]
10.5 - 4. Biomaterials as Stem Cell Niches for Cardiac Cell Therapy [Seite 189]
10.5.1 - 4.1 Cardiac Cell Therapy [Seite 189]
10.5.2 - 4.2 Biomaterial Scaffolds for Cardiac Cell Therapy [Seite 190]
10.6 - 5. Conclusions [Seite 192]
10.7 - References [Seite 193]
11 - The Integrated Role of Biomaterials and Stem Cells in Vascular Regeneration [Seite 199]
11.1 - Abstract [Seite 199]
11.2 - 1. Introduction [Seite 200]
11.3 - 2. Stem Cells for Vascular Regeneration [Seite 201]
11.3.1 - 2.1 Vascular Development of ECs and SMCs from Pluripotent Stem Cells [Seite 201]
11.3.2 - 2.2 Stem-cell-derived Vascular Cells [Seite 203]
11.3.2.1 - 2.2.1 Stem-cell-derived ECs [Seite 203]
11.3.2.1.1 - Endothelial Progenitor Cells [Seite 205]
11.3.2.1.2 - ECs Derived from ESC and iPSC Populations [Seite 206]
11.3.2.2 - 2.2.2 Stem-cell-derived SMCs [Seite 207]
11.4 - 3. Biomimetic Scaffolds for Vascular Regeneration [Seite 208]
11.4.1 - 3.1 General Requirements for Biomimetic Scaffolds [Seite 208]
11.4.2 - 3.2 Polymeric Biomimetic Scaffolds [Seite 209]
11.4.3 - 3.3 Scaffold Types [Seite 213]
11.4.3.1 - 3.3.1 Hydrogels [Seite 213]
11.4.3.2 - 3.3.2 Electrospun Fibers [Seite 213]
11.4.3.3 - 3.3.3 Other Scaffolds [Seite 214]
11.4.4 - 3.4 Vascular Engineering Scaffold Properties [Seite 214]
11.4.4.1 - 3.4.1 Degradation Properties [Seite 214]
11.4.4.2 - 3.4.2 Substrate Topography [Seite 215]
11.4.4.3 - 3.4.3 Mechanical Stimulation [Seite 215]
11.5 - 4. Inclusion of Vascular Stem and Somatic Cells into Biomaterials [Seite 216]
11.5.1 - 4.1 Biomaterials to Engineer Blood Vessels [Seite 216]
11.5.2 - 4.2 Biomaterials to Deliver Cells to Host Vasculature [Seite 217]
11.5.3 - 4.3 Biomaterials to Induce Differentiation [Seite 217]
11.6 - 5. Future Perspectives [Seite 218]
11.7 - 6.Conclusion [Seite 219]
11.8 - References [Seite 219]
12 - Synthetic Niches for Stem Cell Differentiation into T cells [Seite 228]
12.1 - Abstract [Seite 228]
12.2 - 1. Introduction [Seite 229]
12.3 - 2. The T Cell Niche [Seite 230]
12.3.1 - 2.1 T Cell Receptor Gene Rearrangement [Seite 232]
12.3.2 - 2.2 T Cell Microenvironment [Seite 232]
12.4 - 3. T Cell Differentiation Through Co-culture [Seite 234]
12.5 - 4. T Cell Differentiation Through Immobilization of Notch Ligands [Seite 237]
12.5.1 - 4.1 T Cell Differentiation Through Plate Immobilization [Seite 238]
12.5.2 - 4.2 T Cell Differentiation Through Notch--Ligand Presenting Microbeads [Seite 240]
12.6 - 5. Generation of Antigen-specific T Cells from Stem Cells [Seite 240]
12.6.1 - 5.1 Retroviral Transduction of T Cell Receptors [Seite 241]
12.6.2 - 5.2 T Cell Differentiation in a Three-dimensional Matrix [Seite 243]
12.7 - Acknowledgments [Seite 245]
12.8 - References [Seite 246]
13 - Understanding Hypoxic Environments: Biomaterials Approaches to Neural Stabilization and Regeneration after Ischemia [Seite 249]
13.1 - Abstract [Seite 249]
13.2 - 1. Ischemic Brain Damage in Adult and Neonatal Humans [Seite 250]
13.3 - 2. Response of NSPCs to Ischemic Brain Damage [Seite 250]
13.4 - 3. NSPC Implants to Treat Ischemic Brain Damage [Seite 252]
13.5 - 4. NSPC Isolation and Culture: State-of-the-Art [Seite 253]
13.6 - 5. Biomaterials Use in NSPC Applications: State-of-the-Art [Seite 255]
13.7 - 6. Current Challenges in Biomaterials for NSPC Applications [Seite 258]
13.8 - 7. Potential of Biomaterials for Reverse-engineering NSPC Microenvironments [Seite 259]
13.8.1 - 7.1 Neurosphere Culture [Seite 259]
13.8.2 - 7.2 The Stem Cell Niche [Seite 260]
13.8.3 - 7.3 ''Physiological Hypoxia'' and Hypoxic/Ischemic Injury [Seite 261]
13.9 - 8. Conclusions [Seite 264]
13.10 - Acknowledgments [Seite 265]
13.11 - References [Seite 265]
14 - Biomaterial Applications in the Adult Skeletal Muscle Satellite Cell Niche: Deliberate Control of Muscle Stem Cells and Muscle Regeneration in the Aged Niche [Seite 277]
14.1 - Abstract [Seite 277]
14.2 - 1. Introduction [Seite 278]
14.3 - 2. Skeletal Muscle is Regenerated and Maintained by Muscle Stem Cells [Seite 280]
14.3.1 - 2.1 Delta/Notch Signaling Leads to Activation and Proliferation of Satellite Cells [Seite 280]
14.3.2 - 2.2 Wnt Signaling Cues Myogenic Progenitor Cells to Differentiate [Seite 280]
14.4 - 3. The Aged Skeletal Muscle Niche Impairs Normal Regeneration: TGF- beta 1 Signaling Maintains Satellite Cell Quiescence and Leads to Scar Tissue Formation [Seite 282]
14.5 - 4. Toolbox to Combat TGF- beta 1-induced Aging of Satellite Cell Niche [Seite 285]
14.6 - 5. Biomaterials to the Rescue: Proposed Strategies for Adult Skeletal Muscle Regeneration [Seite 287]
14.6.1 - 5.1 Engineering an In Vitro Niche for Robust Skeletal Muscle Regeneration [Seite 287]
14.6.1.1 - 5.1.1 Alignment of In Vitro Skeletal Muscle Fibers [Seite 289]
14.6.1.2 - 5.1.2 Effects of Synthetic Niche Stiffness on Skeletal Muscle Regeneration [Seite 290]
14.6.1.3 - 5.1.3 Electrical Stimulation of Tissue-engineered Skeletal Muscle [Seite 290]
14.6.1.4 - 5.1.4 Vascularization of Tissue-engineered Skeletal Muscle [Seite 291]
14.6.1.5 - 5.1.5 Natural Skeletal Muscle Niches: Mimicking the In Vivo Environment [Seite 292]
14.6.2 - 5.2 Biomaterial Strategies to Combat Aging of the Muscle Stem Cell Niche [Seite 294]
14.6.2.1 - 5.2.1 Gene and Drug Delivery Methods to Promote Skeletal Muscle Regeneration [Seite 294]
14.6.2.2 - 5.2.2 Novel Targeting Strategies for TGF- beta 1 Inhibition [Seite 295]
14.6.2.2.1 - A biomaterial platform for regulating TGF- beta 1 levels to 'young' levels in the aged niche [Seite 295]
14.6.3 - 5.3 Satellite Cells and Muscle Stem Cells: Biomaterials to Help Determine Who is Who [Seite 297]
14.6.4 - 5.4 Use of Biomaterials in Tissue Engineering Applications [Seite 299]
14.7 - 6. Conclusion [Seite 299]
14.8 - Acknowledgments [Seite 299]
14.9 - References [Seite 299]
15 - Author Index [Seite 311]
2 - Contents [Seite 7]
3 - Engineering ECM Complexity into Biomaterials for Directing Cell Fate [Seite 9]
3.1 - Abstract [Seite 9]
3.2 - 1. Cell--ECM Interactions [Seite 9]
3.2.1 - 1.1 ECM Composition and Signaling [Seite 10]
3.2.2 - 1.2 ECM Regulation [Seite 11]
3.2.2.1 - 1.2.1 Proteolytic Processing of the ECM [Seite 11]
3.2.2.2 - 1.2.2 Mechanochemical Translation of Cell-binding ECM Domains [Seite 13]
3.3 - 2. ECM and the Stem Cell Niche [Seite 16]
3.3.1 - 2.1 Integrins: A Sign of ''Stemness'' [Seite 16]
3.3.2 - 2.2 Neural Stem Cells and Integrin/ECM Alterations [Seite 17]
3.3.2.1 - 2.2.1 Integrin and ECM Profile During Neural Development [Seite 17]
3.3.2.2 - 2.2.2 ECM and Integrin Profile in Adult Neural Stem Cell Niche [Seite 18]
3.3.2.3 - 2.2.3 Functional Role of ECM/Integrin Interactions [Seite 19]
3.4 - 3. Current Biomaterials Approaches [Seite 20]
3.4.1 - 3.1 Biomimetic Approaches [Seite 20]
3.4.2 - 3.2 Engineering Protein Variants [Seite 21]
3.4.3 - 3.3 Future Directions for Biomaterials as Stem Cell Niches [Seite 22]
3.5 - References [Seite 23]
4 - Functional Biomaterials for Controlling Stem Cell Differentiation [Seite 27]
4.1 - Abstract [Seite 27]
4.2 - 1. Introduction [Seite 28]
4.2.1 - 1.1 Emergence of Stem Cell Engineering in Regenerative Medicine [Seite 28]
4.2.2 - 1.2 Stem Cell Sources [Seite 28]
4.3 - 2. Stem Cell Expansion and Differentiation Using Biomaterials [Seite 29]
4.3.1 - 2.1 Roles of ECM in Stem Cell Differentiation [Seite 29]
4.3.2 - 2.2 Mimicking ECM with Synthetic Biomaterials [Seite 30]
4.3.2.1 - 2.2.1 Mimicking the Biophysical and Biochemical Properties of ECM [Seite 30]
4.3.2.1.1 - Functionalization of Synthetic Substrates with ECM Derived Ligands [Seite 31]
4.3.2.2 - 2.2.2 Effects of the Cell--Matrix Interface [Seite 31]
4.3.2.2.1 - Surface Chemistry and Interfacial Energy [Seite 31]
4.3.2.3 - 2.2.3 Mineralization of Matrix Materials [Seite 37]
4.3.2.3.1 - Mineralization of Polymeric Matrices [Seite 38]
4.3.2.3.2 - Effect of Mineralization on Cell Adhesion, Proliferation and Differentiation [Seite 38]
4.3.2.4 - 2.2.4 Mechanical Properties [Seite 40]
4.3.3 - 2.3 Biomaterial Based Delivery of Soluble Factors for 3D Cell Culture [Seite 40]
4.3.3.1 - 2.3.1 Incorporation of Bioactive Agents into Matrix Materials [Seite 40]
4.3.3.2 - 2.3.2 Effects of Controlled Delivery of Bioactive Agents on Stem Cell Differentiation [Seite 42]
4.3.3.2.1 - Delivery of Bioactive Agents to Embryonic Stem Cells [Seite 42]
4.3.3.2.2 - Tissue Specific Differentiation of Stem Cells Using Delivery of Bioactive Agents [Seite 44]
4.3.4 - 2.4 In Vivo Applications [Seite 45]
4.3.5 - 2.5 Future Perspectives [Seite 46]
4.4 - Acknowledgments [Seite 47]
4.5 - References [Seite 47]
5 - Integration of Biomaterials into 3D Stem Cell Microenvironments [Seite 53]
5.1 - Abstract [Seite 53]
5.2 - 1. Introduction [Seite 53]
5.2.1 - 1.1 Culture in Two or Three Dimensions [Seite 55]
5.2.2 - 1.2 Strategies for Biomaterial Control of the 3D Microenvironment [Seite 55]
5.3 - 2. Scaffolds [Seite 56]
5.4 - 3. Encapsulation [Seite 59]
5.5 - 4. Microcarriers and Microparticles [Seite 60]
5.5.1 - 4.1 Microcarriers [Seite 61]
5.5.2 - 4.2 Microparticles [Seite 61]
5.6 - 5. Summary and Conclusions [Seite 63]
5.7 - References [Seite 63]
6 - Stem Cell Interaction with Topography [Seite 68]
6.1 - Abstract [Seite 68]
6.2 - 1. Introduction [Seite 68]
6.2.1 - 1.1 Extracellular Topography [Seite 69]
6.2.2 - 1.2 Nanotopography [Seite 70]
6.3 - 2. Nanofabrication Techniques [Seite 71]
6.4 - 3. Stem Cells Reception to Topography [Seite 75]
6.4.1 - 3.1 Embryonic Stem Cells [Seite 75]
6.4.2 - 3.2 Neural Progenitor Cells/Neural Stem Cells [Seite 77]
6.4.3 - 3.3 Mesenchymal Stem Cells [Seite 78]
6.5 - 4. Making Sense of Physical Cues in the Extracellular Matrix: Mechanotransduction [Seite 81]
6.5.1 - 4.1 Introduction to the ECM [Seite 81]
6.5.2 - 4.2 Mechanotransduction: A Direct Connection? [Seite 82]
6.5.3 - 4.3 Connecting with the ECM: Cell--Matrix Interactions [Seite 82]
6.5.4 - 4.4 Integrins and Focal Adhesions: Inside Out and Outside In [Seite 84]
6.5.5 - 4.5 Cytoskeleton: Force Transmission [Seite 85]
6.5.5.1 - 4.5.1 Cell Exerting Forces on the Underlying Substrate [Seite 85]
6.5.6 - 4.6 Filopodia: Probing the ECM [Seite 86]
6.5.7 - 4.7 Nucleus: Gene Regulation [Seite 87]
6.6 - 5. Conclusion [Seite 87]
6.7 - References [Seite 88]
7 - The Nanofiber Matrix as an Artificial Stem Cell Niche [Seite 95]
7.1 - Abstract [Seite 95]
7.2 - 1. The Stem Cell Niche [Seite 95]
7.3 - 2. Nanoscale Topography in the Extracellular Matrix [Seite 97]
7.4 - 3. Methods to Generate Nanofibrous Matrices [Seite 98]
7.4.1 - 3.1 Electrospinning [Seite 98]
7.4.2 - 3.2 Self-assembly [Seite 100]
7.4.3 - 3.3 Solution Phase Separation [Seite 102]
7.4.4 - 3.4 Comparison of Nanofiber Generation Methods [Seite 104]
7.5 - 4. Nanofibrous Matrices for Stem Cell Expansion [Seite 105]
7.5.1 - 4.1 Nanofiber-mediated Expansion of Human Hematopoietic Stem Cells (HSCs) [Seite 105]
7.5.2 - 4.2 Nanofiber-mediated Expansion of Neural Stem Cells (NSCs) [Seite 108]
7.5.3 - 4.3 Nanofiber-mediated Expansion of Embryonic Stem Cells (ESCs) [Seite 108]
7.5.4 - 4.4 Nanofiber-mediated Expansion of Mesenchymal Stem Cells (MSCs) [Seite 109]
7.6 - 5. Nanofiber Matrices for Differentiation of Stem Cells [Seite 109]
7.6.1 - 5.1 Nanofiber-mediated Stem Cell Differentiation into Neuronal Lineages [Seite 110]
7.6.2 - 5.2 Nanofiber-mediated Stem Cell Differentiation into Chondrogenic and Osteogenic Lineages [Seite 112]
7.6.3 - 5.3 Nanofiber-mediated Stem Cell Differentiation into Myogenic Lineage [Seite 114]
7.7 - 6. Nanofibrous Matrices for Stem Cell Delivery [Seite 115]
7.8 - 7. Summary [Seite 117]
7.9 - References [Seite 118]
8 - Micropatterned Hydrogels for Stem Cell Culture [Seite 125]
8.1 - Abstract [Seite 125]
8.2 - 1. Introduction: Application of Biomaterial Technologies to Stem Cell Research [Seite 126]
8.3 - 2. Stem Cells [Seite 128]
8.3.1 - 2.1 MSC General Characteristics [Seite 128]
8.3.2 - 2.2 MSC Differentiation and Plasticity [Seite 129]
8.4 - 3. Hydrogels [Seite 130]
8.4.1 - 3.1 Natural Versus Synthetic Polymers [Seite 131]
8.4.2 - 3.2 Gelation Mechanisms [Seite 131]
8.4.2.1 - 3.2.1 Radical Chain Polymerization [Seite 132]
8.4.2.2 - 3.2.2 Chemical Cross-linking [Seite 132]
8.4.3 - 3.3 Functionalization of Hydrogels [Seite 132]
8.4.3.1 - 3.3.1 Biodegradable Hydrogels [Seite 132]
8.4.3.2 - 3.3.2 Biomimetic hydrogels [Seite 133]
8.5 - 4. Micropatterning [Seite 133]
8.5.1 - 4.1 Microfabrication Technology [Seite 134]
8.5.2 - 4.2 Applications in Hydrogel Patterning [Seite 135]
8.5.2.1 - 4.2.1 Photolithography [Seite 135]
8.5.2.2 - 4.2.2 Laser-scanning lithography [Seite 136]
8.5.2.3 - 4.2.3 Stop-flow Lithography [Seite 137]
8.5.2.4 - 4.2.4 Optofluidic Maskless Lithography [Seite 138]
8.5.2.5 - 4.2.5 Photodegradation [Seite 139]
8.5.2.6 - 4.2.6 Micromolding [Seite 140]
8.5.2.7 - 4.2.7 Two-dimensional Templating [Seite 141]
8.6 - 5. Micropatterning Hydrogels with Embedded Cells [Seite 141]
8.6.1 - 5.1 Culture of One Cell Type [Seite 142]
8.6.1.1 - 5.1.1 Cell Viability [Seite 142]
8.6.1.2 - 5.1.2 Cell Migration (and Morphology) [Seite 143]
8.6.1.3 - 5.1.3 Cell Differentiation [Seite 145]
8.6.2 - 5.2 Culture of Multiple Cell Types [Seite 145]
8.6.2.1 - 5.2.1 Microfluidics [Seite 145]
8.6.2.2 - 5.2.2 Bioreactors [Seite 147]
8.6.2.3 - 5.2.3 Micromolding [Seite 147]
8.6.2.4 - 5.2.4 Stop-flow Lithography [Seite 148]
8.7 - 6.Future Outlook [Seite 148]
8.8 - References [Seite 149]
9 - Microengineering Approach for Directing Embryonic Stem Cell Differentiation [Seite 159]
9.1 - Abstract [Seite 159]
9.2 - 1. Introduction [Seite 159]
9.3 - 2. Control of the Cellular Microenvironment [Seite 161]
9.3.1 - 2.1 Cell--cell Contacts [Seite 161]
9.3.2 - 2.2 Cell--soluble Factor Interactions [Seite 162]
9.3.3 - 2.3 Cell--extracellular Matrix Interactions [Seite 163]
9.4 - 3. Microengineering the Environment [Seite 164]
9.4.1 - 3.1 Microfluidic Platforms for Controlling Cell--soluble Factor Interactions [Seite 165]
9.4.2 - 3.2 Controlled Microbioreactors [Seite 166]
9.4.3 - 3.3 Surface Micropatterning for Controlling Cell--cell Contacts [Seite 167]
9.4.4 - 3.4 High-throughput Microarrays for Screening Microenvironments [Seite 169]
9.4.5 - 3.5 Three Dimensional Scaffolds for Culturing ESCs [Seite 170]
9.4.6 - 3.6 Tissue Engineering Using Assembly of Microengineered Building Blocks [Seite 170]
9.5 - 4. Conclusions [Seite 172]
9.6 - References [Seite 173]
10 - Biomaterials as Stem Cell Niche: Cardiovascular Stem Cells [Seite 178]
10.1 - Abstract [Seite 178]
10.2 - 1. Introduction [Seite 179]
10.3 - 2. Adult Cardiovascular Stem Cells and Their Niches [Seite 179]
10.3.1 - 2.1 Cardiac Stem Cells [Seite 179]
10.3.2 - 2.2 Endothelial Progenitor Cells [Seite 181]
10.3.3 - 2.3 Mural Cell Progenitors/Mesenchymal Stem Cells [Seite 182]
10.3.4 - 2.4 Adult Cardiovascular Stem Cell Niches [Seite 183]
10.4 - 3. Biomaterials as Stem Cell Niches for 3D Cell Culture [Seite 184]
10.4.1 - 3.1 3D Cell Culture Systems for Pluripotent Stem Cells [Seite 184]
10.4.2 - 3.2 3D Cell Culture Systems for Adult Stem Cells [Seite 187]
10.5 - 4. Biomaterials as Stem Cell Niches for Cardiac Cell Therapy [Seite 189]
10.5.1 - 4.1 Cardiac Cell Therapy [Seite 189]
10.5.2 - 4.2 Biomaterial Scaffolds for Cardiac Cell Therapy [Seite 190]
10.6 - 5. Conclusions [Seite 192]
10.7 - References [Seite 193]
11 - The Integrated Role of Biomaterials and Stem Cells in Vascular Regeneration [Seite 199]
11.1 - Abstract [Seite 199]
11.2 - 1. Introduction [Seite 200]
11.3 - 2. Stem Cells for Vascular Regeneration [Seite 201]
11.3.1 - 2.1 Vascular Development of ECs and SMCs from Pluripotent Stem Cells [Seite 201]
11.3.2 - 2.2 Stem-cell-derived Vascular Cells [Seite 203]
11.3.2.1 - 2.2.1 Stem-cell-derived ECs [Seite 203]
11.3.2.1.1 - Endothelial Progenitor Cells [Seite 205]
11.3.2.1.2 - ECs Derived from ESC and iPSC Populations [Seite 206]
11.3.2.2 - 2.2.2 Stem-cell-derived SMCs [Seite 207]
11.4 - 3. Biomimetic Scaffolds for Vascular Regeneration [Seite 208]
11.4.1 - 3.1 General Requirements for Biomimetic Scaffolds [Seite 208]
11.4.2 - 3.2 Polymeric Biomimetic Scaffolds [Seite 209]
11.4.3 - 3.3 Scaffold Types [Seite 213]
11.4.3.1 - 3.3.1 Hydrogels [Seite 213]
11.4.3.2 - 3.3.2 Electrospun Fibers [Seite 213]
11.4.3.3 - 3.3.3 Other Scaffolds [Seite 214]
11.4.4 - 3.4 Vascular Engineering Scaffold Properties [Seite 214]
11.4.4.1 - 3.4.1 Degradation Properties [Seite 214]
11.4.4.2 - 3.4.2 Substrate Topography [Seite 215]
11.4.4.3 - 3.4.3 Mechanical Stimulation [Seite 215]
11.5 - 4. Inclusion of Vascular Stem and Somatic Cells into Biomaterials [Seite 216]
11.5.1 - 4.1 Biomaterials to Engineer Blood Vessels [Seite 216]
11.5.2 - 4.2 Biomaterials to Deliver Cells to Host Vasculature [Seite 217]
11.5.3 - 4.3 Biomaterials to Induce Differentiation [Seite 217]
11.6 - 5. Future Perspectives [Seite 218]
11.7 - 6.Conclusion [Seite 219]
11.8 - References [Seite 219]
12 - Synthetic Niches for Stem Cell Differentiation into T cells [Seite 228]
12.1 - Abstract [Seite 228]
12.2 - 1. Introduction [Seite 229]
12.3 - 2. The T Cell Niche [Seite 230]
12.3.1 - 2.1 T Cell Receptor Gene Rearrangement [Seite 232]
12.3.2 - 2.2 T Cell Microenvironment [Seite 232]
12.4 - 3. T Cell Differentiation Through Co-culture [Seite 234]
12.5 - 4. T Cell Differentiation Through Immobilization of Notch Ligands [Seite 237]
12.5.1 - 4.1 T Cell Differentiation Through Plate Immobilization [Seite 238]
12.5.2 - 4.2 T Cell Differentiation Through Notch--Ligand Presenting Microbeads [Seite 240]
12.6 - 5. Generation of Antigen-specific T Cells from Stem Cells [Seite 240]
12.6.1 - 5.1 Retroviral Transduction of T Cell Receptors [Seite 241]
12.6.2 - 5.2 T Cell Differentiation in a Three-dimensional Matrix [Seite 243]
12.7 - Acknowledgments [Seite 245]
12.8 - References [Seite 246]
13 - Understanding Hypoxic Environments: Biomaterials Approaches to Neural Stabilization and Regeneration after Ischemia [Seite 249]
13.1 - Abstract [Seite 249]
13.2 - 1. Ischemic Brain Damage in Adult and Neonatal Humans [Seite 250]
13.3 - 2. Response of NSPCs to Ischemic Brain Damage [Seite 250]
13.4 - 3. NSPC Implants to Treat Ischemic Brain Damage [Seite 252]
13.5 - 4. NSPC Isolation and Culture: State-of-the-Art [Seite 253]
13.6 - 5. Biomaterials Use in NSPC Applications: State-of-the-Art [Seite 255]
13.7 - 6. Current Challenges in Biomaterials for NSPC Applications [Seite 258]
13.8 - 7. Potential of Biomaterials for Reverse-engineering NSPC Microenvironments [Seite 259]
13.8.1 - 7.1 Neurosphere Culture [Seite 259]
13.8.2 - 7.2 The Stem Cell Niche [Seite 260]
13.8.3 - 7.3 ''Physiological Hypoxia'' and Hypoxic/Ischemic Injury [Seite 261]
13.9 - 8. Conclusions [Seite 264]
13.10 - Acknowledgments [Seite 265]
13.11 - References [Seite 265]
14 - Biomaterial Applications in the Adult Skeletal Muscle Satellite Cell Niche: Deliberate Control of Muscle Stem Cells and Muscle Regeneration in the Aged Niche [Seite 277]
14.1 - Abstract [Seite 277]
14.2 - 1. Introduction [Seite 278]
14.3 - 2. Skeletal Muscle is Regenerated and Maintained by Muscle Stem Cells [Seite 280]
14.3.1 - 2.1 Delta/Notch Signaling Leads to Activation and Proliferation of Satellite Cells [Seite 280]
14.3.2 - 2.2 Wnt Signaling Cues Myogenic Progenitor Cells to Differentiate [Seite 280]
14.4 - 3. The Aged Skeletal Muscle Niche Impairs Normal Regeneration: TGF- beta 1 Signaling Maintains Satellite Cell Quiescence and Leads to Scar Tissue Formation [Seite 282]
14.5 - 4. Toolbox to Combat TGF- beta 1-induced Aging of Satellite Cell Niche [Seite 285]
14.6 - 5. Biomaterials to the Rescue: Proposed Strategies for Adult Skeletal Muscle Regeneration [Seite 287]
14.6.1 - 5.1 Engineering an In Vitro Niche for Robust Skeletal Muscle Regeneration [Seite 287]
14.6.1.1 - 5.1.1 Alignment of In Vitro Skeletal Muscle Fibers [Seite 289]
14.6.1.2 - 5.1.2 Effects of Synthetic Niche Stiffness on Skeletal Muscle Regeneration [Seite 290]
14.6.1.3 - 5.1.3 Electrical Stimulation of Tissue-engineered Skeletal Muscle [Seite 290]
14.6.1.4 - 5.1.4 Vascularization of Tissue-engineered Skeletal Muscle [Seite 291]
14.6.1.5 - 5.1.5 Natural Skeletal Muscle Niches: Mimicking the In Vivo Environment [Seite 292]
14.6.2 - 5.2 Biomaterial Strategies to Combat Aging of the Muscle Stem Cell Niche [Seite 294]
14.6.2.1 - 5.2.1 Gene and Drug Delivery Methods to Promote Skeletal Muscle Regeneration [Seite 294]
14.6.2.2 - 5.2.2 Novel Targeting Strategies for TGF- beta 1 Inhibition [Seite 295]
14.6.2.2.1 - A biomaterial platform for regulating TGF- beta 1 levels to 'young' levels in the aged niche [Seite 295]
14.6.3 - 5.3 Satellite Cells and Muscle Stem Cells: Biomaterials to Help Determine Who is Who [Seite 297]
14.6.4 - 5.4 Use of Biomaterials in Tissue Engineering Applications [Seite 299]
14.7 - 6. Conclusion [Seite 299]
14.8 - Acknowledgments [Seite 299]
14.9 - References [Seite 299]
15 - Author Index [Seite 311]
