Cardiac Extracellular Matrix: Fundamental Science to Clinical Applications

252 Pages·2018·5.62 MB·English

by  Eric G. Schmuck

Advances in Experimental Medicine and Biology 1098
Eric G. Schmuck · Peiman Hematti 
Amish N. Raval Editors
Cardiac
Extracellular
Matrix
Fundamental Science to
Clinical Applications
Advances in Experimental Medicine
and Biology
Volume 1098
Editorial Board:
IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research,
Orangeburg, NY, USA
JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA
RODOLFO PAOLETTI, University of Milan, Milan, Italy
NIMA REZAEI, Tehran University of Medical Sciences, Children’s Medical
Center Hospital, Tehran, Iran
More information about this series at http://www.springer.com/series/5584
Eric G. Schmuck • Peiman Hematti
Amish N. Raval
Editors
Cardiac Extracellular Matrix
Fundamental Science to Clinical Applications
Editors
Eric G. Schmuck Peiman Hematti
School of Medicine & Public Health School of Medicine & Public Health
University of Wisconsin-Madison University of Wisconsin-Madison
Madison, WI, USA Madison, WI, USA
Amish N. Raval
School of Medicine & Public Health
University of Wisconsin-Madison
Madison, WI, USA
ISSN 0065-2598 ISSN 2214-8019 (electronic)
Advances in Experimental Medicine and Biology
ISBN 978-3-319-97420-0 ISBN 978-3-319-97421-7 (eBook)
https://doi.org/10.1007/978-3-319-97421-7
Library of Congress Control Number: 2018954646
© Springer Nature Switzerland AG 2018
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For their unwavering support and
encouragement, I dedicate this book to my
wife, Katie and my children, Owen and
Lillian.
Eric
To my wife, Shirin, and my daughters
Neeloufar and Faranak,
For their Endless Love and Never-ending
Support.
Peiman
With loving adoration and with warm
gratitude for their support of me, I dedicate
this book to the strong women of my life,
Nilam, Serena, Kirin, and Layla.
Amish
Introduction
Cardiac extracellular matrix (ECM) forms the structural and biochemical foundation
of the heart. Historically, cardiac ECM was thought to be an inert web of fibrous
proteins, providing structural support and synergizing myocyte contraction from the
cellular to the organ level. It is now understood that cardiac ECM plays a much
broader foundational role by directing cell survival, migration, proliferation, anoi-
kis, apoptosis, and inflammatory responses. Although all the mechanisms by which
cardiac ECM regulates cell behavior are not fully understood, variables such as
stiffness, architecture, availability of integrin-binding domains, and the presence of
bioactive molecules have been shown to play important roles.
Our evolving understanding of the complex nature of cardiac ECM has led to
important discoveries in the areas of cardiac development, normal cardiac ECM
deposition and maintenance, cardiac ECM-associated pathologies, and the potential
therapeutic value of cardiac ECM in regenerative medicine. As our understanding of
cardiac ECM has grown, so has the potential to manipulate and/or harness cardiac
ECM for bioengineering, tissue engineering, and therapeutic applications. Cardiac
ECM applications include in vitro culture systems for pharmaceutical testing, and
development of cardiac ECM and cardiac ECM inspired materials as stand-alone
therapeutics or in combination with various therapeutic cell types as a means to
regenerate damaged or lost heart tissue. Whole decellularized hearts have been used
as a framework for growing new hearts. This approach, combined with induced
pluripotent stem cell technology, may one day result in personalized whole heart
transplants.
This book explores a broad range of topics related to cardiac ECM. Topics range
from the basic structural and biochemical properties of cardiac ECM to translational
topics including bioengineering and therapeutic application. Finally, this book
incorporates important clinical considerations including manufacturing and clinical
trial design to transferring cardiac ECM technologies from academia to the private
sector for further clinical development. The editors would like to sincerely thank all
of the authors who contributed to the completion of this book. Without their
outstanding contributions, this book would not have been possible.
vii
Contents
1 Biomechanical Properties and Mechanobiology
of Cardiac ECM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Michael Nguyen-Truong and Zhijie Wang
2 Imaging the Cardiac Extracellular Matrix . . . . . . . . . . . . . . . . . . . . . . 21
Michael A. Pinkert, Rebecca A. Hortensius, Brenda M. Ogle,
and Kevin W. Eliceiri
3 Animal Models and Cardiac Extracellular Matrix Research . . . . . . . 45
Timothy A. Hacker
4 Applications of Cardiac Extracellular Matrix
in Tissue Engineering and Regenerative Medicine . . . . . . . . . . . . . . . 59
Mark C. Daley, Spencer L. Fenn, and Lauren D. Black III
5 Whole Cardiac Tissue Bioscaffolds . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Karis R. Tang-Quan, Nicole A. Mehta, Luiz C. Sampaio,
and Doris A. Taylor
6 Natural Sources of Extracellular Matrix for Cardiac Repair . . . . . . 115
Keith L. Spinali and Eric G. Schmuck
7 Cardiac Extracellular Matrix Modification
as a Therapeutic Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Mikayla L. Hall and Brenda M. Ogle
8 Extracellular Matrix for Myocardial Repair . . . . . . . . . . . . . . . . . . . . 151
Jenna L. Dziki and Stephen F. Badylak
9 Role of Extracellular Matrix in Cardiac Cellular Therapies . . . . . . . 173
Peiman Hematti
10 Regulation of Regenerative Medicine Products . . . . . . . . . . . . . . . . . . 189
Adrian P. Gee
ix
x CCoonntteennttss
11 Clinical Trial Design for Investigational
Cardio-Regenerative Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Amish N. Raval
12 Regenerative Medicine Venturing at the University-Industry
Boundary: Implications for Institutions, Entrepreneurs,
and Industry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Adam J. Bock and David Johnson
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
About the Editors
Eric G. Schmuck, PhD is a senior scientist in the

Division of Cardiovascular Medicine at the University of
Wisconsin-Madison School of Medicine and Public
Health where he leads multidisciplinary research teams
focused on bringing regenerative medicine therapies to
the clinic. He received his PhD in Human Physiology
from the University of Wisconsin-Madison and is an
expert in cardiac extracellular matrix and translational
research models, specifically focusing on cardiac regen-
eration. His major research interests are in cardiac extra-
cellular matrix, bioengineering, and regenerative medicine
therapies for the heart. He has authored numerous peer-
reviewed manuscripts and book chapters in the regenera-
tive medicine field and holds multiple patents on cardiac
extracellular matrix technologies. Finally, he is a co-
founder and chief scientific officer of Cellular Logistics
Inc., a biotech company developing innovative biomate-
rial solutions to enhance stem cell retention for the treat-
ment of advanced cardiovascular disease.

Peiman Hematti, MD is professor of Medicine in the

Section of Hematology/Oncology, University of
Wisconsin-Madison School of Medicine and Public
Health, with joint appointments in departments of pedi-
atrics, surgery, and biomedical engineering. He is
director of the Clinical Hematopoietic Cell Processing
Laboratory and medical director of Apheresis and
Hematopoietic Cell Collection facility at the University
of Wisconsin-Madison. As a bone marrow stem cell
transplant physician, his major clinical research interest
is in immunology of transplantation and use of novel
xi
xii About the Editors
cellular therapies for malignant and nonmalignant dis-
orders, including the use of bone marrow stem cells in
cardiovascular medicine. His current laboratory
research focuses on immunobiology of stem cell trans-
plantation with a special focus on investigating the
immunomodulatory and anti-inflammatory properties
of macrophages, including their interactions with bio-
materials used in regenerative medicine. He has been a
coauthor in more than 100 peer-reviewed manuscripts
and 10 book chapters and has been coeditor of two
other books in the field of stem cells and regenerative
medicine. He has been inventor of several patents
issued and filed in the field of cellular therapy and
regenerative medicine. He is a co-founder and chair of
the Scientific Advisory Board for Cellular Logistics
Inc.

Amish N. Raval, MD is an associate professor of

Medicine and Biomedical Engineering at the University
of Wisconsin. He received his MD at the University of
Western Ontario, where he completed Internal Medicine
and Cardiology Residency. He subsequently completed
his Interventional Cardiology Fellowship at Georgetown
University/Washington Hospital Center, and later, he
joined the National Heart, Lung, and Blood Institute,
Bethesda. Thereafter, he became a faculty member at
the University of Wisconsin School of Medicine and
Public Health where he is director of Clinical
Cardiovascular Research. He is an accomplished inter-
ventional cardiologist with expertise in structural heart
and endovascular and coronary interventions. His trans-
lational research is focused on therapeutic delivery of
biologic agents, including stem cells and scaffolds for
cardiac and vascular disease. He has numerous peer-
reviewed publications, national scientific statements,
and patents in this field. He is the principal investigator
of >12 cardiovascular regenerative medicine clinical tri-
als ranging from Phase 1 to Phase 3. He has served as a
scientific advisor for several biotech companies and is
chairman of the Board for Cellular Logistics Inc., which
is a biotech company that is developing innovative bio-
material solutions to enhance stem cell retention for the
treatment of advanced cardiovascular disease.