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Beschreibung

Stem Cells, Craniofacial Development and Regeneration is an introduction to stem cells with an emphasis on their role in craniofacial development. Divided into five sections, chapters build from basic introductory information on the definition and characteristics of stem cells to more indepth explorations of their role in craniofacial development. Section I covers embryonic and adult stem cells with a focus on the craniofacial region, while sections II-IV cover the development and regeneration of craniofacial bone, tooth, temporomandibular joint, salivary glands and muscle. Concluding chapters describe the current, cutting-edge research utilizing stem cells for craniofacial tissue bioengineering to treat lost or damaged tissue.

The authoritative resource for dentistry students as well as craniofacial researchers at the graduate and post-graduate level, Stem Cells, Craniofacial Development and Regeneration explores the rapidly expanding field of stem cells and regeneration from the perspective of the dentistry and craniofacial community, and points the way forward in areas of tissue bioengineering and craniofacial stem cell therapies.

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Table of Contents

Title Page

Copyright

Contributors

Preface

Part I: Development and Regeneration of Craniofacial Tissues and Organs

Chapter 1: Molecular blueprint for craniofacial morphogenesis and development

1.1 Introduction

1.2 Ectoderm: Neural Induction

1.3 Ectoderm: Neurulation

1.4 Head induction

1.5 Ectoderm: Neural Crest Cells

1.6 Ectoderm: Placodes

1.7 Mesoderm: Muscle

1.8 Mesoderm: Endothelial Cells

1.9 Endoderm: oral cavity

1.10 Conclusions and Perspectives

Acknowledgments

References

Chapter 2: Cranial neural crest cells in craniofacial tissues and organs

2.1 Introduction

2.2 Palate development

2.3 Tooth development

2.4 Tongue development

2.5 Conclusions and perspectives

References

Chapter 3: Craniofacial intramembranous bone development and regeneration

3.1 Introduction

3.2 Initial stages of craniofacial bone development

3.3 Osteoblast differentiation, function, and fate

3.4 Osteoclast differentiation and function

3.5 Cellular coordination of bone deposition and resorption

3.6 Intramembranous bone growth, modeling, remodeling, suture formation, and function

3.7 Intramembranous bone regeneration

3.8 Conclusions and future directions

References

Chapter 4: Temporomandibular Joint Development

4.1 Introduction

4.2 Development of the TMJ

4.3 Mammalian condyle is made of secondary cartilage

4.4 Many genes are expressed similarly in the developing condyle and primary cartilages

4.5 Tissue interactions play critical roles in TMJ development

4.6 Regulation of TMJ development by transcription factors

4.7 Growth factor–mediated signaling pathways play multiple roles in TMJ development

4.8 Regulation of TMJ development by extracellular matrix

4.9 Contribution of extrinsic factors to TMJ development

4.10 Conclusions

Acknowledgment

References

Chapter 5: Craniofacial muscle development

5.1 Introduction

5.2 Somitic myogenesis and myogenic regulatory hierarchies

5.3 Cranial mesoderm

5.4 Genetic control of extraocular muscle development

5.5 Branchiomeric myogenesis

5.6 Genetic control of branchiomeric myogenesis

5.7 Pharyngeal mesoderm: connecting head and heart muscle development

5.8 Visceral origins of branchiomeric skeletal muscles

5.9 Cranial neural crest patterns developing craniofacial muscle

5.10 Conclusions and Perspectives

Acknowledgments

References

Chapter 6: Tooth morphogenesis and renewal

6.1 Introduction

6.2 Developmental anatomy of tooth formation

6.3 Regulation of tooth morphogenesis and dental signaling centers

6.4 Dental cell lineages and their differentiation

6.5 Tooth renewal

6.6 Dental stem cells, tooth renewal, and prospects for tooth regeneration

6.7 Conclusions and future directions

References

Chapter 7: Reptilian Tooth Regeneration

7.1 Introduction

7.2 How ancestral is tooth regeneration in amniotes?

7.3 Basal amniotes in both mammalian and reptilian lineages could replace their teeth

7.4 General process of tooth development and replacement in squamate reptiles

7.5 The relationship between the successional lamina and tooth regeneration

7.6 Molecular controls of the reformation of the successional lamina

7.7 The successional lamina recapitulates gene expression patterns of the early dental lamina

7.8 Signaling pathway interactions during formation of the successional lamina

7.9 Potential involvement of other factors in successional lamina reformation or survival: Ectodysplasin and Fibroblast Growth factors

7.10 Stem Cells in squamate tooth replacement

7.11 Challenges for the future

References

Chapter 8: Tooth Root Development

8.1 Introduction

8.2 Structure and Composition of Tooth Root Tissues

8.3 Developmental Processes in Root Formation

8.4 Signaling and Inductive Influences in Root Development

8.5 Conclusions and Future Directions

Acknowledgments

References

Chapter 9: Systems Biology of Early Tooth Development

9.1 Introduction

9.2 Systems biology of E-M signaling dynamics during early odontogenesis

9.3 Conclusions and future directions

Acknowledgments

References

Part II: Stem Cells and their Niches in Craniofacial Tissues

Chapter 10: Stem cells, induced pluripotent stem cells, and their differentiation to specified lineage fates

10.1 Introduction

10.2 Definition and concepts of stem cells

10.3 Pluripotent stem cells

10.4 Differentiation of stem cells for regeneration and therapy

10.5 Applications using cells derived from pluripotent stem cells

10.6 Limitations and Perspective

Acknowledgments

References

Chapter 11: Bone Marrow Mesenchymal Stem Cells

11.1 Introduction

11.2 Bone Marrow Stromal System

11.3 Characterization of Bone Marrow MSC

11.4 Perivascular Properties of Human Bone Marrow MSC

11.5 Immunomodulatory Properties

11.6 Bone Marrow MSC-Based Therapies for Treating Craniofacial Defects

11.7 Concluding Remarks

References

Chapter 12: Adipose tissue–derived stem cells and their regeneration potential

12.1 Introduction

12.2 Characterization of Stromal Vascular Fraction Cells and Adipose tissue–derived Stromal and Stem Cells

12.3 Findings from Craniofacial PreClinical Animal Models

12.4 Future Directions

Acknowledgments

References

Chapter 13: Skeletal muscle stem cells: their origin and niche factors

13.1 Introduction

13.2 Embryonic Myogenesis

13.3 Satellite Cell Niche

13.4 Growth Factors

13.5 Differences in craniofacial and limb muscles

13.6 Conclusions and future perspective

Acknowledgments

References

Chapter 14: Stem cells in salivary gland development and regeneration

14.1 Introduction

14.2 Salivary gland development

14.3 The clinical need for progenitor cells

14.4 Multiple progenitors participate in development and regeneration

14.5 Communication between epithelial progenitors and their niche is essential for gland development and regeneration

14.6 Clinical translation of biological processes into regenerative medicine approaches

14.7 Future directions in the salivary gland field

References

Chapter 15: Stem and progenitor cells of dental and gingival tissue origin

15.1 Introduction

15.2 Dental pulp

15.3 Periodontal ligament

15.4 Apical papilla

15.5 Dental neural crest–derived progenitor cells

15.6 Dental follicle

15.7 Gingival tissue–derived MSCs

15.8 Conclusions

Acknowledgments

References

Chapter 16: Regulation and differentiation potential of dental mesenchymal stem cells

16.1 Introduction

16.2 Differentiation potential of dental mesenchymal stem cells

16.3 Regulation of stem cell differentiation by T-cells

16.4 Molecular regulation of dental mesenchymal stem cell differentiation

16.5 Transcriptional regulation of dental mesenchymal stem cell differentiation

16.6 Epigenetic regulation of dental mesenchymal stem cell differentiation by microRNAs

16.7 Physical factors in dental mesenchymal stem cell differentiation

16.8 Summary

Acknowledgments

References

Chapter 17: An incisive look at stem cells: the mouse incisor as an emerging model for tooth renewal

17.1 Introduction

17.2 From replacement to ever-growing teeth

17.3 The epithelial stem cell niche in the continuously growing mouse incisor

17.4 Concluding remarks and open questions

References

Chapter 18: Mesenchymal stem cell niches in rodent tooth pulp

18.1 Introduction

18.2 rodent incisor mesenchymal stem cell niche(s)

18.3 molar mesenchymal stem cell niche

18.4 Future Prospects

Acknowledgments

References

Part III: Stem Cell-Mediated Craniofacial Tissue Bioengineering

Chapter 19: Bone bioengineering: scaffolds, growth factors, and stem cells

19.1 Introduction

19.2 Scaffolds

19.3 Growth Factors

19.4 Stem Cells

19.5 Enabling Technologies

19.6 Application of Scaffolds, Growth Factors, and Stem Cells

19.7 Future Considerations

Acknowledgments

References

Chapter 20: Craniofacial tissue bioengineering and regeneration by endogenous stem cells

20.1 Introduction

20.2 Cell migration and recruitment

20.3 Cell homing models

20.4 Regeneration by cell homing

20.5 Summary

Acknowledgments

References

Chapter 21: Stem Cell–Based Bioengineering of Craniofacial Bone

21.1 Introduction

21.2 Mesenchymal Stromal Cells

21.3 Adipose-Derived Stromal Cells

21.4 Induced Pluripotent Stem Cells

21.5 Stem Cells and Gene Therapy

21.6 Conclusions

Acknowledgment

References

Chapter 22: Muscle tissue engineering approaches

22.1 Introduction

22.2 Skeletal muscle regeneration

22.3 Tissue engineering strategies

22.4 Conclusions and future perspectives

References

Chapter 23: Engineering of dental tissues: scaffolds and preclinical models

23.1 Introduction

23.2 Scaffolds in dental tissue engineering

23.3 Models for dental tissue engineering

23.4 Conclusions

References

Chapter 24: Whole-tooth engineering and cell sources

24.1 Introduction

24.2 Whole-tooth organ engineering using embryonic dental cells

24.3 Cell sources for engineering of the enamel organ

24.4 Mesenchymal cell sources

24.5 Requirements for mesenchymal cells to be used for tooth engineering

24.6 Conclusions

Acknowledgments

References

Chapter 25: Bioengineering of functional teeth

25.1 Introduction

25.2 Tooth development

25.3 Whole-tooth regeneration as a future organ-replacement regenerative therapy

25.4 Functional Tooth Organ Replacement in vivo

25.5 Conclusions and future directions

Acknowledgments

References

Chapter 26: Pulp and Dentin Regeneration

26.1 Introduction

26.2 Revitalization of immature tooth: pulp healing and repair

26.3 Pulp–dentin engineering and regeneration: ectopic model

26.4 Pulp–dentin engineering and regeneration: orthotopic model

26.5 Future Perspectives

Acknowledgments

References

Chapter 27: Bioengineering of roots and periodontal tissues

27.1 Introduction

27.2 Bioroot engineering

27.3 Bioengineering of periodontal tissues

27.4 Conclusions and future directions

Acknowledgments

References

Chapter 28: Periodontal bioengineering strategies: the present status and some developing trends

28.1 Introduction

28.2 Periodontal bioengineering

28.3 Biomaterials for periodontal bioengineering

28.4 Growth factors and their delivery

28.5 Stem cells for periodontal bioengineering

28.6 Periodontal bioengineering strategies

28.7 Challenges and future directions

Acknowledgments

References

Index

Copyright © 2013 by Wiley-Blackwell. All rights reserved.

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Published by John Wiley & Sons, Inc., Hoboken, New Jersey.

Published simultaneously in Canada.

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Library of Congress Cataloging-in-Publication Data:

Stem cells in craniofacial development and regeneration / edited by George

T.-J. Huang, Irma Thesleff.

p. cm.

Includes bibliographical references and index.

ISBN 978-1-118-27923-6 (cloth)

1. Regeneration (Biology). 2. Bone regeneration. 3. Guided bone

regeneration. 4. Stem cells. I. Huang, George T.-J. II. Thesleff, Irma.

QH499.S816 2013

571.8'89--dc23

2012028577

Contributors

John Abramyan, Ph.D., Postdoctoral Fellow, Department of Oral Health Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
Barbara D. Boyan, Ph.D., Professor, Price Gilbert, Jr. Chair in Tissue Engineering, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
Yang Chai, D.D.S., Ph.D., George and MaryLou Boone Professor of Craniofacial Biology, Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
Fa-Ming Chen, Ph.D., D.D.S., Professor and Dental Surgeon, Department of Periodontology and Oral Medicine, and Translational Research Team, School of Stomatology, Fourth Military Medical University, Shaanxi, China
Mo Chen, Ph.D., Associate Research Scientist, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
YiPing Chen, Ph.D., Professor, Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana
Choko Cho, Ph.D., Postdoctoral Fellow, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Michael T. Chung, B.S., Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California
Gang Ding, D.D.S., Ph.D., Associate Professor, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing, China
Mildred C. Embree, D.M.D., Ph.D., Assistant Professor, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Jifan Feng, Ph.D., Craniofacial Development and Stem Cell Biology, Biomedical Research Centre, and MRC Centre for Transplantation, Dental Institute, King's College, London, UK; Postdoctoral Research Associate, Center for Craniofacial Molecular Biology Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
Brian L. Foster, Ph.D., National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland
Jonathan A. Garlick, D.D.S., Ph.D., Professor, Division of Cancer Biology and Tissue Engineering, Department of Oral and Maxillofacial Pathology, School of Dental Medicine, Tufts University, Boston, Massachusetts
Jeffrey Gimble, M.D., Ph.D., Professor, Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana
Rolando Gittens, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
Sander Grefte, Ph.D., Postdoctoral Researcher, Department of Biochemistry, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Stan Gronthos, Ph.D., Professor, Mesenchymal Stem Cell Laboratory, Department of Haematology, University of Adelaide, Adelaide, South Australia, Australia
Monica Grova, B.S., Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California
Shuping Gu, D.D.S., Ph.D., Assistant Research Professor, Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana
Christopher D. Hermann, Ph.D., Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
Kyle J. Hewitt, Ph.D., Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts
Joshua W. K. Ho, Ph.D., Instructor, Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Matthew P. Hoffman, B.D.S., Ph.D., National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland
George T.-J. Huang, D.D.S., M.S.D., D.Sc., Professor, Director for Stem Cells and Regenerative Therapies, Department of Bioscience Research, College of Dentistry, The University of Tennessee Health Science Center, Memphis, Tennessee
Jeong S. Hyun, M.D., Postdoctoral Research Fellow, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California
John A. Jansen, D.D.S., Ph.D., Professor, Department of Biomaterials, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Andrew H. Jheon, D.D.S., Ph.D., Assistant Adjunct Professor, Department of Orofacial Sciences and Program in Craniofacial and Mesenchymal Biology, University of California–San Francisco, San Francisco, California
Nan Jiang, D.D.S., Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Yan Jin, Ph.D., D.D.S., Professor, Research and Development Center for Tissue Engineering, Fourth Military Medical University, Shaanxi, China
Maria Jussila, M.Sc., Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
Emma Juuri, D.D.S., M.Sc. Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
L. Keller, INSERM UMR 1109, Team “Osteoarticular and Dental Regenerative NanoMedicine,” Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France
Robert G. Kelly, Ph.D., Investigator, Developmental Biology Institute of Marseilles–Luminy, Aix–Marseille University, Marseille, France
Ophir D. Klein, M.D., Ph.D., Associate Professor, Departments of Orofacial Sciences and Pediatrics, Program in Craniofacial and Mesenchymal Biology, and Institutes for Human Genetics and Regeneration Medicine, University of California–San Francisco, San Francisco, California
Kimi Kong, Ph.D., Associate Research Scientist, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
S. Kuchler-Bopp, Ph.D., Chargée de recherche, INSERM UMR 1109, Team “Osteoarticular and Dental Regenerative NanoMedicine,” Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France
Chang Hun Lee, Ph.D., Associate Research Scientist, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Christopher S. D. Lee, Ph.D., Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
Hervé Lesot, Ph.D., Investigator, INSERM UMR 1109, Team “Osteoarticular and Dental Regenerative NanoMedicine,” Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France
Yi Liu, D.D.S., Ph.D., Associate Professor, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing, China
David D. Lo, M.D., Postdoctoral Research Fellow, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California
Isabelle M. A. Lombaert, Ph.D., National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland
Michael T. Longaker, M.D., M.B.A., Deane P. and Louise Mitchell Professor, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California; and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California
Richard L. Maas, M.D., Ph.D., Professor, Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Jeremy J. Mao, D.D.S., Ph.D., Professor and Zegarelli Endowed Chair, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Avital Mendelson, Ph.D., Postdoctoral Fellow, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Frederic Michon, Ph.D., Academy Fellow, Institute of Biotechnology, Developmental Biology Program, University of Helsinki, Helsinki, Finland
Daniel T. Montoro, B.S., Life Science Research Associate, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California
Christian Morsczeck, M.Sc., Ph.D., Private lecturer, Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany
Misako Nakashima, D.D.S., Ph.D., Investigator, Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Obu, Aichi, Japan
Hemin Nie, Ph.D., Postdoctoral Fellow, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Francisco H. Nociti, Jr., D.D.S., Ph.D., National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland; State University of Campinas School of Dentistry, Piracicaba, São Paulo, Brazil
Daniel J. O'Connell, Ph.D., Postdoctoral Fellow, Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Rene Olivares-Navarrete, D.D.S., Ph.D., Senior Research Scientist, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
Carolina Parada, D.M.D, Ph.D, Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
Adelina Plachokova, D.D.S., Ph.D., Assistant Professor, Department of Biomaterials, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Maryam Rezai Rad, Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana
David P. Rice, B.D.S., F. Orth., Ph.D., Professor, Department of Orthodontics, Institute of Dentistry, University of Helsinki, and Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland
Ritva Rice, Ph.D., Postdoctoral Researcher, Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
Joy M. Richman, Ph.D., D.M.D., Professor, Department of Oral Health Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
Zvi Schwartz, D.M.D., Ph.D., Professor, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
Kerstin Seidel, Ph.D., Postdoctoral Fellow, Department of Orofacial Sciences and Program in Craniofacial and Mesenchymal Biology, University of California–San Francisco, San Francisco, California
Yulia Shamis, Ph.D., Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts
Paul T. Sharpe, Ph.D., Professor, Craniofacial Development and Stem Cell Biology, Biomedical Research Centre and MRC Centre for Transplantation, Dental Institute, King's College, London, UK
Songtao Shi, D.D.S., Ph.D., Professor, Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
Martha J. Somerman, D.D.S., Ph.D., National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland
Irma Thesleff, Ph.D., Professor, Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
Paul A. Trainor, Ph.D., Investigator, Stowers Institute for Medical Research, Kansas City, Missouri; and Professor, Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas
Takashi Tsuji, Ph.D., Professor, Research Institute for Science and Technology, and Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan; and Organ Technologies Inc., Tokyo, Japan
Johannes W. Von den Hoff, Ph.D., Assistant Professor, Department of Orthodontics and Craniofacial Biology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
X. Frank Walboomers, Ph.D., Associate Professor, Department of Biomaterials, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Derrick C. Wan, M.D., Assistant Professor, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California
Lei Wang, Ph.D., D.D.S., Postdoctoral Fellow, Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California; and Faculty of Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Shaanxi, China
Songlin Wang, D.D.S., Ph.D., Professor, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing, China
Fulan Wei, D.D.S., Ph.D., Lecturer, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing, China
John A. Whitlock, Ph.D., Postdoctoral Fellow, Department of Oral Health Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
Xing Yan, D.D.S., Ph.D., Postdoctoral Fellow, Department of Endodontics, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts, and Associate Chief Physician, Department of Stomatology, Beijing Friendship Hospital (Second Clinical School), Capital Medical University, Beijing, China
Fang Yang, Ph.D., Assistant Professor, Department of Biomaterials, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Shaomian Yao, Ph.D., Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana
Na Yu, D.D.S., Department of Biomaterials, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Ying Zheng, D.D.S., Ph.D., Postdoctoral Fellow, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Jian Zhou, D.D.S., Ph.D., Postdoctoral Fellow, Center for Craniofacial Regeneration, Columbia University Medical Center, New York, New York
Xiao-Ying Zou, D.D.S., M.D., Postdoctoral Fellow, Department of Endodontics, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts, and Department of Cariology, Endodontology, and Operative Dentistry, School and Hospital of Stomatology, Peking University, Beijing, China

Preface

This book project was motivated by the need to present in one place current knowledge on the regulation of normal development of craniofacial tissues, and on the characteristics of tissue-specific stem cells and their potential use in bioengineering/regeneration of craniofacial tissues and organs. It has become obvious that knowledge of the mechanisms of normal development will be essential when tissues and organs are attempted to generate from stem and progenitor cells. In particular, developmental biology research has unraveled the key roles of cell–cell interactions in all developmental processes, and identified specific signal molecules as the molecular mediators of these interactions. These same signals are the main tools in guiding stem cell proliferation and differentiation in the process of tissue regeneration via bioengineering technologies.

In recent years there have been huge advances in stem cell biology and in characterization of pluripotent stem cells and tissue-specific stem cells. The discovery of reprogramming differentiated cells to pluripotent stem cells has opened the possibility of using the patient's own cells for a variety of biomedical applications. Various adult stem cells have also been tested for their tissue regeneration potential. At the same time, major strides have been made in the field of tissue engineering. Engineered organs have been transplanted into patients to restore damaged ones. Strategies and study models for engineering and regenerating craniofacial tissues and organs, including teeth, have also shed light on their future clinical applications.

In the first part of the book, there are nine chapters summarizing the current knowledge on developmental mechanisms involved in selected craniofacial tissues and organs. During embryogenesis, the morphogenesis and cell differentiation are intimately linked. The complex shapes of organs, as well as the specialized cell types, are generated in concert step-by-step from progenitor cells.

The second part elaborates on stem cells and their niches. It covers the general area of stem cells, including embryonic stem cells and induced pluripotent stem cells. The physiological renewal and regeneration of tissues is based on stem cells. Postnatal stem cells of various tissue origins are reviewed with an emphasis on their potential application for craniofacial tissue regeneration. Tissue-specific stem cells, such as salivary gland stem cells and tooth stem cells, have been identified and characterized in craniofacial tissues. The details on stem cells and their differentiation are best known in continuously renewing tissues such as bone. However, stem cells are also present in adult permanent teeth, for example, pulp tissue, functioning as the source of replacement odontoblasts to form new dentin.

The third part gives an overview of ongoing research on bioengineering of craniofacial tissues, including bone, muscle, dental tissues, periodontal tissues, and teeth. The use of scaffolds, growth factors, and stem cells are the key elements for engineered tissue regeneration.

In the case of teeth, one scenario is to grow new teeth from progenitor cells by applying knowledge of the mechanisms of their normal development. The regeneration of many types of craniofacial tissues has been tested and has achieved success in small and large animals. Some of the regeneration technologies are being studied in clinical trials. It appears inevitable that tissue regeneration and regenerative medicine will become a mainstream medical practice in the near future.

We are very grateful to have such group of authors reviewing the latest work in their fields, including their own work, and sharing their expert views on future possibilities and challenges. Everyone we asked agreed to contribute to the book. All are respected specialists in their fields. We are thankful to all of them for writing the excellent chapters and we are extremely happy with the end result. We hope that students, as well as scientists in the field, young and advanced, will find this book useful.

George Huang

Irma Thesleff

Part I

Development and Regeneration of Craniofacial Tissues and Organs

Chapter 1: Molecular blueprint for craniofacial morphogenesis and development

Paul A. Trainor

Stowers Institute for Medical Research, Kansas City, Missouri, and University of Kansas Medical Center Kansas City Kansas

1.1 Introduction

The vertebrate head is a sophisticated assemblage of cranial specializations, including the central and peripheral nervous systems and viscero-, chondro-, and neurocraniums, and each must be properly integrated with musculature, vasculature, and connective tissue. Anatomically, the head is the most complex part of the body, and all higher vertebrates share a common basic plan or craniofacial blueprint that is established during early embryogenesis. This process begins during gastrulation and requires the coordinated integration of each germ layer tissue (i.e., ectoderm, mesoderm, and endoderm) and its derivatives in concert with the precise regulation of cell proliferation, migration, and differentiation for proper craniofacial development (Figs. 1.1 and 1.2). For example, the appropriate cranial nerves must innervate the muscles of mastication, which, via tendon attachment to the correct part of the mandible, collectively articulate jaw opening and closing. In addition, each of these tissues must be sustained nutritionally and remain oxygenated and thus are intimately associated with the vasculature as part of a fully functioning oral apparatus.

Figure 1.1 Specification of ectoderm, neural crest, placodes, mesoderm, and endoderm. In situ hybridization (A, B, D–I) or lacZ staining (C) of E8.5–9.5 mouse embryos as indicators of differentiation of ectoderm (A, Bmp4), neural crest cells (B, Sox10; C, Wnt1cre-R26R), ectodermal placodes (D and E, Eya2), endoderm (F, Pax1), mesoderm (G and I, Tbx1), and endothelial cells (H, Vegfr2).

Figure 1.2 Formation of the nervous system, skeleton, musculature, and vasculature. Immunostaining (A, C, and E) and histochemical stainining (B and D) as indicators of formation of the peripheral nervous system (A, E10.5, Tuj1), cartilage (B, E15.5, alcian blue), vasculature (C, E9.5, PECAM), skeletal bone and cartilage (E18.5, alizarin red/alcian blue), and muscle (E18.5, MHC).

Given this complexity, it is not surprising that a third of all congenital defects affect the head and face (Gorlin et al., 1990). Improved understanding of the etiology and pathogenesis of head and facial birth defects and their potential prevention or repair depends on a thorough appreciation of normal craniofacial development. But what are the signals and mechanisms that establish each of these individual cells and tissues and govern their differentiation and integration? In this chapter specification of the major cell lineages, tissues, and structures that establish the blueprint for craniofacial development is described, as well as the interactions and integration that are essential for normal functioning throughout embryonic as well as adult life.

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