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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_6018_Библиотеки_им_академика_М_И_Перельмана.pdf
Biological Approaches to Spinal Disc
Repair and Regeneration for Clinicians
Roger Härtl, MD
Professor of Neurological Surgery
Director of Spinal Surgery
Director, Weill Cornell Medicine Center for Comprehensive Spine Care
Attending Neurosurgeon
Weill Cornell Medicine, New York-Presbyterian Hospital
New York, New York
Lawrence J. Bonassar, PhD
Professor
Meinig School of Biomedical Engineering
Sibley School of Mechanical and Aerospace Engineering
Cornell University
Ithaca, New York
82 illustrations
Thieme
New York • Stuttgart • Delhi • Rio de Janeiro
Executive Editor: Timothy Hiscock
Managing Editor: Sarah Landis
Director, Editorial Services: Mary Jo Casey
Editorial Assistant: Nikole Connors
Production Editor: Naamah Schwartz
International Production Director: Andreas Schabert
International Marketing Director: Fiona Henderson
International Sales Director: Louisa Turrell
Director of Sales, North America: Mike Roseman
Senior VicePresident andChief OperatingOfficer: Sarah Vanderbilt
President: Brian D. Scanlan
Library of Congress Cataloging-in-Publication Data
Names: Härtl, Roger, editor. | Bonassar, Lawrence J., editor.
Title: Biological approaches to spinal disc repair and regeneration
for clinicians / [edited by] Roger Härtl, Lawrence J. Bonassar.
Description: New York : Thieme, [2017] | Includes bibliographical
references and index.
Identifiers: LCCN 2016057426| ISBN 9781626232501 (hardback) |
ISBN 9781626232518 (eISBN)
Subjects: | MESH: Intervertebral Disc Degeneration–complications |
Intervertebral Disc–physiopathology | Intervertebral Disc
Degeneration–therapy | Low Back Pain–etiology | Low Back
Pain–therapy |
Total Disc Replacement–methods
Classification: LCC RD771.B217 | NLM WE 740 | DDC 617.564–dc23
LC record available at https://lccn.loc.gov/2016057426
Important note: Medicine is an ever-changing science undergoing continual development. Research and clinical experience are
continually expanding our knowledge, in particular our knowledge of proper treatment and drug therapy. Insofar as this book
mentions anydosage or application, readers may rest assured that
the authors, ed itors, and publishers have made every effort to
ensure that such references are in accordance with the state of
knowledge at the time of production of the book.
Nevertheless, this does not involve, imply, or express any
guarantee or responsibility on the part of the publishers in respect
to any dosage instructions and forms of applications stated in the
book. Every user is requested to examine carefully the manufac-
turers’ leaflets accompanying each drug and to check, if necessary
in consultation with a physician or specialist, whether the dosage
schedulesmentioned therein or the contraindicationsstatedby the
manufacturers differ from the statements made in the present
book. Such examination is particularly important with drugs that
are either rarely used or have been newly released on the market.
Every dosageschedule or every form of application used isentirely
atthe user’sownrisk andresponsibility.The authorsand publishers
request every user to report to the publishers any discrepancies or
inaccuracies noticed. If errors in this work are found after publication, errata will be posted at www.thieme.com on the product
description page.
Some of the product names, patents, and registered designs
referred to in this book are in fact registered trademarks or proprietary names even though specific reference to this fact is not
always made in the text. Therefore, the appearance of a name
without designation as proprietary is not to be construed as a
representation by the publisher that it is in the public domain.
© 2017 Thieme Medical Publishers, Inc.
Thieme Publishers New York
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ISBN 978-1-62623-250-1
Also available as an e-book:
eISBN 978-1-62623-251-8
This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the
narrow limits set by copyright legislation without the publisher’s
consent is illegal and liableto prosecution.This appliesin particular
to photostatreproduction, copying, mimeographing or duplication
of any kind, translating, preparation of microfilms, and electronic
data processing and storage.
Contents
Foreword ............................................................................................ vii
Preface.............................................................................................. viii
Contributors ........................................................................................ ix
Part I: Basics
1. The Human Spinal Disc: Relevant Anatomy and Physiology
Julien Tremblay Gravel, Fahad H. Abduljabbar, Jean Ouellet, and Lisbet Haglund
..................................... 2
2. Pathophysiology of Disc Disease: Disc Degeneration............................................ 11
Niloofar Farhang, Joshua Stover, Brandon Lawrence, and Robby D. Bowles
3. Imaging of the Healthy and Diseased Spinal Disc ................................................ 20
Darryl B. Sneag and Hollis G. Potter
4. Biomechanics of the Healthy and Diseased Spine................................................ 30
Hans-Joachim Wilke and Fabio Galbusera
Part II: Experimental Techniques
5. Differences between Human and Animal Discs: Pros and Cons of Current Animal
Models for Preclinical Development of Biological Therapies for Low Back Pain
Jeffrey C. Lotz
............... 38
6. Grading Scales for Disc Degeneration and Regeneration: Clinical and Experimental ......... 48
Peter Grunert
7. Disc Regeneration: In Vitro Approaches and Experimental Results ............................ 54
John T. Martin, Harvey E. Smith, Lachlan J. Smith, and Robert L. Mauck
8. Intervertebral Disc Whole Organ Cultures ....................................................... 66
Marianna Peroglio, Zhen Li, Lorin Michael Benneker, Mauro Alini, and Sibylle Grad
Part III: Treatment Strategies
9. Biological Treatment Approaches: Basic Ideas and Principles
Victor Y. Leung and Kenneth M.C. Cheung
................................... 76
10. Learning from Successes of Tissue Engineering Strategies for Car tilaginous Disorders ...... 82
Stephen R. Sloan, Jr. and Lawrence J. Bonassar
11. Treatment of Degenerative Disc Disease and Disc Regeneration: Proteins and Genes ....... 90
Daisuke Sakai and Jordy Schol
12. Treatment of Degenerative Disc Disease/Disc Regeneration: Growth Factors and
Platelet Rich Plasma
Koichi Masuda and Kenji Kato
.............................................................................. 101
v
Contents
13. Treatment of Degenerative Disc Disease/Disc Regeneration: Stem Cells,
Chondrocytes or Other Cells, and Tissue Engineering
Steven Presciutti and Howard An
......................................... 110
14. Nucleus Replacement and Repair: Autologous Disc Chondrocyte Transplantation ......... 121
Christian Hohaus, Timothy Ganey, and Hans Jörg Meisel
15. Annulus Fibrosus Repair.......................................................................... 128
Olivia M. Torre, Michelle A. Cruz, Andrew C. Hecht, and James C. Iatridis
Part IV: Clinical Experience
16. Summary of Clinical Trials with Biological Treatment Approaches for Spinal Disease
Gernot Lang, Ibrahim Hussain, Micaella Zubkov, Yu Moriguchi, Brenton Pennicooke, Rodrigo Navarro-Ramirez,
and Roger Härtl
...... 140
17. Total Disc Transplantation: Current Results and Future Development ....................... 150
Jason Pui Yin Cheung, Dike Ruan, and Keith D.K. Luk
18. What Have We Learned from Mechanical Total Disc Replacement? ......................... 158
Timothy T. Roberts, Colin M. Haines, and Edward C. Benzel
19. Regulatory Overview: Obtaining Regulatory Approval of a Biological/Cell Product ........ 170
Michaela H. Purcell, Penny J. White, and H. Davis Adkisson
20. What Makes Biological Treatment Strategies and Tissue Engineering for DDD
Interesting to Industry?
Hassan Serhan, Elliott A. Gruskin, and William C. Horton
.......................................................................... 177
Part V: Outlook
21. What Will the Future Bring? Perspectives From Around the World
Howard An, Tony Goldschlager, Claudius Thomé, Luiz Vialle, Jaime Arias Ruiz, William Omar Contreras Lopez, and
Daisuke Sakai
.......................... 184
Appendix A ........................................................................................ 189
Appendix B ........................................................................................ 192
Index ............................................................................................... 197
vi
Foreword
Disc degeneration and regeneration is an important contemporary medical issue of concern for the vast majority of
physicians that manage patients on a daily basis with the
ubiquitous complaint of low back discomfort. We understand that a healthy lifestyle of avoiding excessive weight
gain and exposure to nicotine products as well as getting
daily exercise is beneficial for intervertebral disc homeostasis. We have also made tremendous gains over the last
decade in understanding the genetics of disc degeneration
and the potential for disc regeneration. Research has
allowed us to understand that the disc itself harbors stem
cells that may be activated with appropriate cues and
promoted to proliferate with the correct cocktail of growth
factors yet to be determined. We have recently understood
the importanceof the intervertebral endplateand its ability
to allow and regulate stress transfer as well as nutritional
support to the disc. We have so much further to go in
understanding methods to replenish the disc with viable
cells in an innocuous fashion not to cause iatrogenic discal
injury.
The background for understanding the complex intervertebral disc milieu is wonderfully laid out in this book by
Dr. Roger Härtl and Dr. Lawrence Bonassar. Great thought
wasplaced inorganizing a bookthat introduces notonly the
novice but also the expert in the lab on the anatomy,
pathophysiology and biomechanics of the intervertebral
disc. Interesting insight is provided in understanding the
applicability of chosen animal models that have been
validated as analogous to the human intervertebral disc.
An exploration into our failed attempts in the past of
substituting mechanical disc replacements of the human
disc is discussed in detail and potential avenues for treatment in the future are explored.
The editors’ list ofauthors isa “Who’sWho” in the study
of the intervertebral disc. The book is captivating, as the
subject matteris well thoughtout, theformat iseasy toread,
and the illustrations are striking. This textbook will certainly be a staple in all educational venues such as colleges,
universities, medical schools, clinical residencies and fellowship programs and, most importantly, the basic science
world. I congratulate Dr. Härtl, Dr. Bonassar, all of the wellknown contributing authors throughout the world, and
especiallythe publisher forallowingsuch an insightfulbook
to be created for the benefit of those who suffer from low
back pain.
Alexander R. Vaccaro, MD, PhD, MBA
Richard H. Rothman Professor and Chairman,
Department of Orthopaedic Surgery
Professor of Neurosurgery
Co-Director, Delaware Valley Spinal Cord Injury Center
Co-Chief of Spine Surgery
Sidney KimmelMedical Centerat Thomas Jefferson University
President, Rothman Instit ute
Philadelphia, Pennsylvania
vii
Preface
This book was written to shed light on one of the most
puzzling problems we are facing in medicine today: our
approach tolow backpain (LBP) thatoriginatesfrom degenerative disc disease (DDD). LBP is a leading cause of disability worldwide and has been linked directly and indirectly toDDD. LBP has aglobal lifetime prevalence of almost
40% and a large socioeconomic impact with estimated
annual indirect and direct costs exceeding $100 billion in
the United States alone. There is a genetic component that
puts individuals with a familyhistory of DDD at greater risk
of developing low back or neck pain themselves.
Today we knowthat prevention of andtreatment forany
type of back, neck, or leg pain should always begin with the
adaptation of basic rules of healthy living: weight control,
healthy food, exercises to strengthen core, flexibility and
stretching, and physical activity or therapy. We are successful in treating patients who suffer from pain caused by
nerve root compression: neurogenic claudication, for
example, can be treated successfully with minimally invasive ambulatory surgery. Radicular pain due to disc herniations can be relieved with outpatient procedures. What we
consider “mechanical back pain” due to mechanical instability of the spine can be treated with sometimes complex
spinal reconstruction and stabilization procedures. However, there are two sources of pain and sufferingthat we are
struggling to understand, adequately diagnose, and treat:
muscle and intervertebral disc (IVD). Whereas muscle
physiology has been studied extensively for decades, by
comparison, relatively little is known about the physiology
of IVD.
This book focuses on pain caused by DDD, which we
characterize broadly as “discogenic back pain.” The contributors include the scientific and clinical leaders in the
field. The current surgical treatment options for back pain
resulting from DDD are associated with risks and undesirable long-term effects, and they are clearly unsatisfactory.
Fusion surgery or disc arthroplasty procedures are only
partially successful and probablynot better than, for example, physical therapy and cognitive behavioral interventions. Finding effective treatments for pain stemming from
DDD has been difficult due to its complicated pathophysiology and our incomplete knowledge of the underlying
processes leading to degeneration of the IVD. Many factors
work together to initiate, exacerbate, and maintain the
degenerative process; these include genetic predisposition,
decreased nutrient transport, abnormal biomechanics,
smoking, and the normal wear and tear of the IVD associated with aging. Whereas the relative importance of each
risk factor in initiating DDD is uncertain, these factors
initiate a cascade of molecular mechanisms, leading to the
breakdown of the disc and possibly back pain.
This book is dedicated to the practitioners who treat
patients with back pain and who want to learn about what
is being done at the forefront of basic and translational
science to solve the challenges associated with DDD. We do
not have final answers, but this book will highlight and
explain the many exciting and promising approaches that
arebeing exploredto better understand,diagnose, andtreat
pain and disability deriving from DDD. Ultimately, the
successful approach to the management of back and neck
pain will likely involve a combination of preventive measures such as healthy lifestyle modi fi cations and exercises
to address muscular origin,and minimally invasive surgical
and biological treatment interventions to address more
advanced stages related to DDD.
Lawrence J. Bonassar, PhD
Roger Härtl, MD
viii