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Mesenchymal Cell Activation by
Biomechanical Stimulation and its Clinical
Prospects
Edited By
Nahum Rosenberg
Department of Orthopedic Surgery
Rambam Health Care Campus and Ruth and Bruce Rappaport
Faculty of Medicine
Technion – Israel Institute of Technology
Haifa
Israel
© Bentham Science Publishers – Sharjah, UAE. All Rights Reserved.
Mesenchymal Cell Activation by
Biomechanical Stimulation and its Clinical
Prospective
Editor: Nahum Rosenberg
ISBN (eBook): 978-1-68108-199-1
ISBN (Print): 978-1-68108-200-4
© 2016, Bentham eBooks imprint.
Published by Bentham Science Publishers –
Sharjah, UAE. All Rights Reserved.
First published in 2016.
Acknowledgments:
Declared None.
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DEDICATION
I dedicate this work to my wife Orit and my daughters Ella, Talia and Shelly who
gave me all the peace of mind I needed to accomplish this book.
CONTENTS
Foreword i
Preface iii
Contributors v
CHAPTERS
1. Mechanics of Living Cells – General Aspects 3
Eyal Ginesin, Kamal Hamoud and Nahum Rosenberg
2. Experimental Methods for Mechanical Stimulation of Cells of Mesenchymal
Origin 13
Nahum Rosenberg and Reuben Haber
3. Mechanical Stimulation of Mesenchymal Stem Cells 23
David Nikomarov and Nahum Rosenberg
4. Bio-Mechanical Stimulation of Skin Fibroblasts 35
Yaron Har-Shai, Isaac Zilinsky, Rei Ogawa and Chenyu Huang
5. Mechanotransduction in Osteoblats 49
Yaron Berkovich, Jacob Shapira and Nahum Rosenberg
6. Mechanotransduction in Chondrocytes 59
Marwan Haddad, Jacob Shapira and Nahum Rosenberg
7. Cellular Molecular Pathways in Distraction Osteogenesis 65
Yoav Leiser and Adi Rachmiel
Subject Index 73
i
FOREWORD
During the last two decades there have been many studies demonstrating the responses of cells of
mesenchymal origin (osteoblasts, chondrocytes, fibroblasts, etc.) to mechanical stimulation.
However, due to the use of various experimental methods, it has become difficult to compare the
research data. Many studies implement the variations of the method of cyclic mechanical
stimulation via stretchable membranes onto adherent cells, but other methods exist as well. To
compare the data from different experimental methods the mechanical stimulation should be
characterized by its displacement, frequency and acceleration (or by the wave shape of the applied
force), but in most of the studies neither all this information nor even the common stimulation
parameters for cells activation are apparent.
The previous data demonstrate that cellular deformation affects the cytoskeleton, which results in
the activation of a cascade of secondary messengers that stimulate metabolic or proliferative
response, i.e. mechanotransduction pathways. Unfortunately standardized biomechanical protocols
for the optimal in vitro mechanical stimulation of cells are lacking. This standardization should
provide all the essential biomechanical information, such as an exact specification of a mechanical
force applied, and, if it is cyclic, the mechanical profile specifications should be given.
Additionally information on the cell deformation is required. If this information will be provided
the optimal parameters of the mechanical stimulation will be determined and the presently existing
controversy regarding these parameters will be at least partially settled. This will open the
opportunity for the future more effective and comparable studies for determination of the
intracellular mechanisms involved in cellular mechanotransduction. However presentation of the
current data and knowledge, which are derived from different biomechanical experimental
methods of the cellular mechanotransduction research, should also contribute to the
communication in this expanding research field.
Michael Soudry
Hillel Yafe Medical Center
Hadera
Israel
iii
PREFACE
Skin, bone and cartilage are the important examples of live tissues that respond to mechanical
stimulation and that require it for their metabolic maintenance. The cells in these organs, which are
responsible for matrix regeneration and responsive to mechanical stimulation, are, among others,
the fibroblasts, the osteocytes (osteoblasts) and the chondrocytes (chondroblasts). All these cells
are of the mesenchymal origin and maturate from multipotent mesenchymal stem cells (MSCs). It
was previously shown than MSCs can maturate to one of these cell types when exposed to
appropriate media (osteogenic, chondrogenic, etc.) with the addition of mechanical stimulation
with the optimal characteristic mechanical parameters.
In this book the authors address the special characteristics of the responses of these types of cells
to mechanical stimulation. The process of the cellular mechanical stimulation,
mechanotransduction, is partially similar among these cells, but there are also several very
important differences in mechanical parameters and cellular pathways. The current knowledge on
the characteristic cellular mechanotransduction pathways is expanding. The authors aimed to
concentrate on the description of the more investigated pathways, which are characteristic to each
cell type.
The book starts with the chapters on general aspects of cellular biomechanics and description of
the experimental equipment that is commonly used for the research of cellular
mechanotransduction in vitro in two dimensional cultures, especially when the cells are adherent
to plastic surfaces. The characteristic pathways of mechanotransduction in MSCs, osteoblasts and
osteocytes, chondrocytes and fibroblasts are described in following chapters and eventually a
description of clinical implementation of mechanical stimulation is added with emphasis on
distraction osteogenesis, involving osteoblast stimulation, and on the skin stretching techniques
based on fibroblasts’ stimulation.
The area of cellular mechanotransduction research is still widely open for further research and
discoveries. In this book the authors tried to summarize the current knowledge on
mechanotransduction in the MSCs and the three mature cell types, which are responsible for the
maintenance of tissues that provide body support, cover and movement.
Nahum Rosenberg
Department of Orthopaedic Surgery
Rambam - Health Care Campus and Ruth and Bruce Rappaport Faculty of Medicine
Technion – Israel Institute of Technology
Haifa
Israel
v
CONTRIBUTORS
Berkoviz Yaron
Department of Orthopedic Surgery, Rambam Health Care Campus, POB
9602, Haifa 31096, Israel.
Chenyu Huang
Department of Plastic, Reconstructive and Aesthetic Surgery, Beijing
Tsinghua Changgung Hospital; Medical Center, Tsinghua University,
China.
Ginesin Eyal
Department of Orthopedic Surgery, Rambam Health Care Campus, POB
9602, Haifa 31096, Israel.
Haber Reuben
Department of Orthopedic Surgery, Rambam Health Care Campus, POB
9602, Haifa 31096, Israel.
Haddad Marwan
Department of Orthopedic Surgery, Rambam Health Care Campus, POB
9602, Haifa 31096, Israel.
Hamoud Kamal
Department of Orthopedic Surgery, Rambam Health Care Campus, POB
9602, Haifa 31096, Israel.
Har-Shai Yaron
Department of Plastic Surgery, Carmel Medical Center, .Michal 7 str.,
Haifa 34362, Israel.
Leiser Yoav
Department of Oral and Maxillofacial Surgery, Rambam Health Care
Campus, POB 9602, Haifa 31096, Israel.
Nikomarov David
Department of Orthopedic Surgery, Rambam Health Care Campus, POB
9602, Haifa 31096, Israel.
Rachmiel Adi
Department of Oral and Maxillofacial Surgery, Rambam Health Care
Campus, POB 9602, Haifa 31096, Israel.
Rei Ogawa
Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon
Medical School, Tokyo, Japan.
Rosenberg Nahum
Department of Orthopaedic Surgery, Rambam Health Care Campus,
POB 9602, Haifa 31096, Israel.
Shapira Jacob
Department of Orthopedic Surgery, Rambam Health Care Campus, POB
9602, Haifa 31096, Israel.
Zilinsky Isaac
The Unit of Plastic Surgery, Carmel Medical Center, 7 Michal St., Haifa
3436212, Israel.
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