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Biology and Engineering of Stem Cell Niches

1st Edition - March 22, 2017

Editors: Ajaykumar Vishwakarma, Jeffrey M Karp

Paperback ISBN:

9 7 8 - 0 - 1 2 - 8 0 2 7 3 4 - 9

eBook ISBN:

9 7 8 - 0 - 1 2 - 8 0 2 7 5 6 - 1

Biology and Engineering of Stem Cell Niches covers a wide spectrum of research and current knowledge on embryonic and adult stem cell niches, focusing on the understanding of stem… Read more

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Biology and Engineering of Stem Cell Niches covers a wide spectrum of research and current knowledge on embryonic and adult stem cell niches, focusing on the understanding of stem cell niche molecules and signaling mechanisms, including cell-cell/cell-matrix interactions.

The book comprehensively reviews factors regulating stem cell behavior and the corresponding approaches for understanding the subsequent effect of providing the proper matrix molecules, mechanical cues, and/or chemical cues. It encompasses a variety of tools and techniques for developing biomaterials-based methods to model synthetic stem cell niches in vivo, or to enhance and direct stem cell fate in vitro.

A final section of the book discusses stem cell niche bioengineering strategies and current advances in each tissue type.

Part I. Biology of Stem Cell Niches and Molecular Mechanisms

Chapter 1. The Need to Study, Mimic, and Target Stem Cell Niches

1. Introduction
2. Biology of the Stem Cell Niche
3. Biochemical and Biophysical Regulation of Stem Cell Behavior
4. Mimicking the Stem Cell Niche: Bioengineering Tools and Techniques
5. Bioengineering Specialized Artificial Stem Cell Niches for Clinical Therapies

Chapter 2. Harnessing the Biology of Stem Cells' Niche

1. Introduction
2. Components of the Stem Cell Niche
3. Integrative Networks Regulating the Niche
4. Distinct Niches for Different Stages of Differentiation
5. Neoplastic Transformation and Disturbance of the Tissue Ecosystem
6. Conclusion
Abbreviations and Acronyms
Glossary

Chapter 3. Pluripotent Stem Cell Microenvironment

1. Introduction
2. Pluripotent Cell Microenvironment in the Early Mammalian Embryo
3. Microenvironment of Pluripotent Stem Cells In Vitro
4. Conclusion
Abbreviations and Acronyms
Glossary

Chapter 4. Regulation of Hematopoietic Stem Cell Dynamics by Molecular Niche Signaling

1. Introduction
2. Organization of Hematopoietic Stem Cell Niche in the Bone Marrow
3. Niche Signaling
4. Future Outlook and Challenges
Abbreviations and Acronyms
Glossary

Chapter 5. HSC Niche: Regulation of Mobilization and Homing

1. Introduction
2. HSC Trafficking During Embryonic Development
3. HSC Trafficking in Adult Hematopoiesis
4. New Strategies to Enhance Homing and Engraftment of HSC
5. Techniques to Dissect the Mechanism of HPC Migration
6. Clinical Applications of the Mobilization Agents and Biochemical Factors
7. Conclusion
Glossary

Chapter 6. Neuronal Stem Cell Niches of the Brain

1. Introduction
2. Organization of the Brain's Neuronal Stem Cell Niches
3. Functional Role of the Brain's Neuronal Stem Cell Niches
4. Signaling in the Neural Stem Cell Niche
5. Neural Stem Cell Niche in Aging
6. Conclusion
Abbreviations and Acronyms
Glossary

Chapter 7. Cardiovascular Stem Cell Niche

1. Introduction
2. Myocyte Regeneration and Cardiac Progenitor Cell Niches
3. Lineage Tracing of the Stem Cell Progeny
4. Stem Cells: Studies at the Single-Cell Level
5. Cardiac Progenitor Cell Classes and Their Niches
6. c-kit-CPCs and Their Niches
7. Epicardial Progenitor Cell Niches
8. Mesenchymal Stem Cells and Cardiac Niches
9. Hypoxic Niches
10. Cardiomyocyte Proliferation and the Notch Receptor System
11. Cardiac Niches and the Notch Receptor System
12. Conclusions
Abbreviations and Acronyms
Glossary

Chapter 8. Intestinal Epithelial Lgr5+ Stem Cell Niche and Organoids

1. Introduction
2. Intestinal Stem Cell
3. The Stem Cell Niche
4. Ex Vivo Intestinal Stem Cells Culture—Organoids
5. Application of Organoid System
6. Concluding Remarks

Chapter 9. The Epithelial Stem Cell Niche in Skin

1. Introduction
2. The Adult Skin: A Model to Study Various Epithelial Stem Cells
3. The Multiple Actors in Adult Epithelial Stem Cell Niche in the Skin
4. Do the Niche Cells From Various Locations Regulate the Epithelial Stem Cell Fate Differently?
5. Conclusions
Abbreviations and Acronyms
Glossary

Chapter 10. The Satellite Cell Niche in Skeletal Muscle

1. Introduction
2. The Quiescent Satellite Cell Niche
3. The Activated Satellite Cell Niche
4. Alterations of the Satellite Cell Niche
5. Conclusion
Abbreviations and Acronyms
Glossary

Chapter 11. The Cancer Stem Cell Niche

1. Introduction
2. Cancer Stem Cells and Niche Interactions
3. Cancer Stem Cell Niche Promotes Tumor Growth and Progression
4. The Role of the Cancer Stem Cell Niche in Metastasis
5. Therapeutic Targeting of Cancer Stem Cell Niche
6. Conclusion
Abbreviations and Acronyms
Glossary

Chapter 12. Cellular Senescence and Stem Cell Niche

1. Introduction
2. Cellular Senescence
3. p16INK4a
4. Senescence-Associated Secretory Phenotype
5. Senescence and Tissue Repair
6. Stem Cell Niche
7. Effects of Aging and Senescence on the Stem Cell Niche

Part II. Biochemical and Physical Cues in The Stem Cell Niche Directing Cell Fate

Chapter 13. Matrix Chemistry Controlling Stem Cell Behavior

1. Introduction
2. Effect of Chemical Functional Groups on Stem Cell Behavior
3. Conclusions and Future Directions
Abbreviations and Acronyms
Glossary

Chapter 14. Matrix Growth Factor and Surface Ligand Presentation

1. Introduction
2. Modulating Factor-Mediated Signaling
3. Cell–Cell Ligand Presentation
4. Adhesion Ligand Presentation
5. Synergistic Interaction Between Adhesion Ligands and Soluble Factors
6. Outlook
Abbreviations and Acronyms

Chapter 15. Effect of Matrix Mechanical Forces and Geometry on Stem Cell Behavior

1. The Mechanical Microenvironment of Stem Cells
2. The Influence of Mechanical Forces on Stem Cell Differentiation
3. The Influence of Matrix Geometry and Topography on Stem Cell Behavior
4. How Do Stem Cells Respond to Mechanical Stimuli?
5. Future Directions
Abbreviations and Acronyms

Chapter 16. Wettability Effect on Stem Cell Behavior

1. Introduction
2. The Impact of Interfacial Wettability on Cells
3. The Impact of Interfacial Wettability on Stem Cells
4. Conclusion and Future Directions

Chapter 17. Fluid Flow Control of Stem Cells With Investigation of Mechanotransduction Pathways

1. Introduction
2. Mimicking In Vivo Fluid Flow Environments
3. Fluid Flow Regulation of Stem Cell Function and Fate
4. Fluid Flow-Activated Mechanotransduction Pathways in Stem Cells
5. Conclusions
Abbreviations and Acronyms
Glossary

Chapter 18. Hypoxia Regulation of Stem Cell: Mechanisms, Biological Properties, and Applications

1. Physiological Relevance of Hypoxic Niche in Embryonic and Adult Stem Cells
2. Molecular Mechanism of Hypoxia-Mediated Cellular Response
3. Stem Cell Metabolic Adaptation Under Hypoxia
4. Influence of Hypoxia on Stem Cell Fate
5. Recapitulation of Hypoxia Niche In Vivo and In Vitro
6. Hypoxia-Preconditioning-Enhanced Therapeutic Function After Transplantation
Abbreviations and Acronyms

Part III. Designing Smart Biomaterials to Mimic and Control Stem Cell Niche

Chapter 19. Polymer Design and Development

1. Introduction
2. Natural Polymers for 3D Stem Cell Culture
3. Synthetic Polymers for 3D Stem Cell Culture
4. Smart Polymer Systems for 3D Stem Cell Culture
5. Concluding Remarks
Abbreviations and Acronyms
Glossary

Chapter 20. Design and Development of Ceramics and Glasses

1. Introduction
2. Development of Bioceramics
3. Design of Bioactive Ceramics and Composites
4. Engineering Stem Cell Niches
5. Summary and Future Perspective

Chapter 21. Surface Functionalization of Biomaterials

1. Introduction
2. Surface Modifications of Biomaterials
3. Biological Relevance of Surface Modification for Biomaterials
4. Concluding Remarks
Abbreviations and Acronyms
Glossary

Chapter 22. Biofunctional Hydrogels for Three-Dimensional Stem Cell Culture

1. Introduction
2. Hydrogel Materials
3. Hydrogel Material Properties
4. Engineering Hydrogel Bioactivity
5. Technologies for Hydrogel Production and Assessment
6. Challenges and Future Directions
7. Conclusion
Abbreviations and Acronyms

Chapter 23. Technologies to Engineer Cell Substrate Mechanics in Hydrogels

1. Introduction
2. Microenvironment and Its Stiffness
3. Dimensionality
4. The Determinants of Elastic Properties and Hydrogel Networks
5. ECM as a Substrate for Adhesive Cells
6. Hydrogels to Mimic the In Vivo Microenvironment
7. Natural Hydrogels
8. Synthetic Hydrogels
9. Development of Hydrogel Systems as a Scaffold for Cell-Based Therapies
10. Conclusion and Future Directions
Abbreviations and Acronyms

Chapter 24. Micro- and Nanosurface Patterning Technologies

1. Introduction to Micro- and Nanopatterning Techniques for Cell Culture
2. Introduction to Fabrication Techniques for Nanotopography
3. Nanotopography and Its Applications
4. Conclusion
Abbreviations and Acronyms
Glossary

Chapter 25. Self-Assembled Nanostructures (SANs)

1. Introduction
2. Layer-by-Layer Self-Assembly
3. Fabricating Free-Standing Thin Films Using Layer-by-Layer
4. Layer-by-Layer Coating on Graphene
5. Layer-by-Layer Coating of Nanoscale Liposomes
6. Layer-by-Layer Coating of Nanoparticles
7. Layer-by-Layer Coating of 3D Scaffolds
8. Self-Assembled Nanoparticles
9. Self-Assembled Nanofibers and Nanotubes
10. Conclusion
Abbreviations and Acronyms

Chapter 26. Biomimetic Nanofibers as Artificial Stem Cell Niche

1. Introduction
2. Methods for Preparing Polymeric Nanofibers
3. Control Stem Cell Behaviors Through Biomimetic Nanofibers In Vitro
4. Delivery of Stem Cells With Biomimetic Nanofibers for Tissue Regeneration
5. Concluding Remarks
Abbreviations and Acronyms

Part IV. Bioengineering Strategies to Model Synthetic Stem Cell Niches

Chapter 27. Employing Microfluidic Devices to Induce Concentration Gradients

1. Introduction
2. Engineering Concentration Gradients Using Microtechnology
3. Generating Micro-Engineered Gradients to Control Stem Cell Fate
4. Future Directions
Abbreviations and Acronyms
Glossary

Chapter 28. Engineering Niches for Embryonic and Induced Pluripotent Stem Cells

1. Introduction
2. Niches for Embryonic Stem/Induced Pluripotent Stem Cell Maintenance
3. Niches for Regulation of Differentiation
4. Conclusion and Outlook
Abbreviations and Acronyms
Glossary

Chapter 29. Engineering Niches for Cardiovascular Tissue Regeneration

1. Introduction
2. The Cardiac Microenvironment
3. Cell-Based Cardiac Regenerative Therapy
4. Biomaterial Engineering for Cardiac Regeneration
5. Types of Biomaterials and Their Applications
6. Biomaterial-Based Cardiovascular Devices
7. Future Direction for Cardiac Regeneration
Abbreviations and Acronyms
Glossary

Chapter 30. Engineering Niches for Blood Vessel Regeneration

1. Introduction
2. Elements for Recapitulating the Vascular Regeneration Niche In Vitro
3. Material Design Parameters for Controlling the Vascular Niche
4. Strategies in Engineering Artificial Niches for Vascular Regeneration
5. Inducing Vascularization Through Biomaterials
6. Conclusion and Future Directions
Abbreviations and Acronyms
Glossary

Chapter 31. Engineering Niches for Bone Tissue Regeneration

1. Introduction: The Native Bone Niche
2. Approaches to Control the Stem Cell Niche
3. Conclusions and Future Directions
Abbreviations and Acronyms
Glossary

Chapter 32. Engineering Vascular Niche for Bone Tissue Regeneration

1. Introduction
2. The Bone Tissue Engineering Paradigm: Scaffold, Cells, Bioreactor
3. Strategies to Promote Bone Vascularization
4. Harnessing the Inflammatory Response to Engineer Vascularized Bone
5. Endochondral Ossification and the Hematopoietic Niche
6. Conclusions and Future Directions
Abbreviations and Acronyms
Glossary

Chapter 33. Engineering Niches for Cartilage Tissue Regeneration

1. Introduction: The Native Cartilage Niche
2. Approaches for Engineering the Cartilage Niche
3. Conclusion and Future Directions
Abbreviations and Acronyms
Glossary

Chapter 34. Engineering Niches for Stem and Progenitor Cell Differentiation Into Immune Cells

1. Introduction
2. Hematopoiesis and Niche Signaling
3. 2D Immune Cell Culture Systems
4. Engineering 3D Immune Niche
5. Future Directions and Conclusions
Abbreviations and Acronyms
Glossary

Chapter 35. Engineering Niches for Skin and Wound Healing

Chapter Outline
1. Introduction
2. The Skin Stem Cell Niche From a Wound Healing Perspective
3. Engineering of Skin Stem Cell Niches for Wound Healing
4. Specific Targets for Niche-Based Approaches in the Skin
5. Conclusion
Abbreviations and Acronyms

Chapter 36. Designing Stem Cell Niche for Liver Development and Regeneration

1. Introduction
2. LPCs Fate Selection in Developing and Injured Liver
3. Hepatic Stem Cell Niches
4. Engineering Biomimetic Liver Niches
5. Conclusion
Abbreviations and Acronyms
Glossary

Chapter 37. Engineering the Niche for Intestinal Regeneration

1. Introduction
2. Overview of Intestinal Culture Models and Regenerative Medicine Approaches
3. Tools and Techniques for Engineering the Intestinal Stem Cell Niche
4. Future Directions: Engineering the Niche for Intestinal Modeling and Development of Regenerative Medicine Therapies
5. Conclusions
Abbreviations and Acronyms
Glossary

Ajaykumar Vishwakarma

Dr Ajay Vishwakarma is a researcher in the fields of stem cell bio-engineering, biomaterials, tissue engineering, cancer immunology and immuno-engineering; working with Division of Engineering in Medicine, Department of Medicine, at Brigham and Women’s Hospital, Harvard Medical School and an affiliate at the Harvard-MIT Division of Health Sciences and Technology at the Massachusetts Institute of Technology. Dr Vishwakarma earned a Doctors degree in Dental Surgery at Maharashtra University of Health Sciences and Masters degree in Tissue Engineering at Cardiff University, UK where he primarily studied signaling pathways involved in musculoskeletal repair and regeneration. He continued mesenchymal stem cell and tissue-engineering research during his fellowship in the Khademhosseini laboratory at the Harvard-MIT Division of Health Sciences and Technology, USA. Currently he is pursuing a PhD in Cancer Biology with training in Cancer Immunology at the Carver College of Medicine, University of Iowa in Prof. Weizhou Zhang’s Laboratory, Department of Pathology, Holden Cancer Center wherein he is studying how regulatory T cells impact cancer progression and metastasis in humanized cancer models. He was a recipient of a stem cell training fellowship from CCMB, a CSIR Indian institute, a graduate research fellowship by National Blood Foundation and National Cancer Institute government grant agencies. In addition to the long-term academic interest; he is committed to translating next generation cell-based therapies and has held key industrial positions in Europe and Asia. He is a co-founder of OCTE Technologies, a biotech start-up utilizing cell and tissue engineering technology platform to solve medical problems.

Affiliations and expertise

Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States

Jeffrey M Karp

Dr. Jeff Karp is a leading researcher in the fields of stem cell therapeutics, drug delivery, medical devices,and tissue adhesives. He is an Associate Professor at Brigham and Women’s Hospital, Harvard Medical School, Principal Faculty at the Harvard Stem Cell Institute, and an affiliate faculty at the Broad Institute and at the Harvard-MIT Division of Health Sciences and Technology (where he teaches to MIT-Sloan business school students). He has published >100 peer-reviewed papers (with >11,750 citations) and has given 250 national and international invited lectures and has 65 issued or pending patents. Several technologies developed in his lab have formed the foundation for multiple products on the market and currently under development and for the launch of four companies including Skintifique, Gecko Biomedical, Alivio Therapeutics, Frequency Therapeutics. Karp’s work has been discussed in hundreds of newspapers, online websites, television newscasts, and radio shows around the world including CNN, ABC News, NBC, Boston Globe, LA Times, BBC, Discovery, National Geographic, The Atlantic, The Guardian, American Museum for Natural History, Popular Mechanics, CTV Canada AM. Karp has also appeared multiple times on CBC’s Quirks and Quarks and NPR Science Fridays. The Boston Business Journal recognized him as a Champion in Healthcare Innovation and MIT’s Technology Review Magazine (TR35) also recognized Dr. Karp as being one of the top innovators in the world (3 members from his laboratory have subsequently received this award). His work has been selected by Popular Mechanic's "Top 20 New Biotech Breakthroughs that Will Change Medicine.” He gave a TEDMED talk at the Kennedy Center in DC on bioinspired medical innovation and since 2015 has been a member of the TEDMED Editorial Advisory Board (only member to be elected to the board 3 years in a row). In 2015 and 2016 he received Breakthrough Awards from the Kenneth Rainin Foundation and in 2015 was a commencement speaker in at the University of Toronto. He also serves as a consultant to the Kenneth Rainin Foundation and the Crohn’s and Colitis Foundation on the topic of new technologies for Inflammatory Bowel Disease. He has deep consulting expertise with startups and with several Fortune 500 companies across a wide spectrum of areas including drug delivery, medical devices, consumer healthcare products, and stem cell therapeutics. Dr. Karp was selected as the Outstanding Faculty Undergraduate Mentor among all Faculty at MIT and he received the HST McMahon Mentoring award for being the top mentor of Harvard-MIT students. To date, 18 trainees from his laboratory have secured faculty positions and several have transitioned into impactful careers in pharma, biotech, medtech, and venture capital.

Affiliations and expertise

Assistant Professor, Co-Director of Regenerative Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; Principal Investigator, Harvard Stem Cell Institute