Table Of ContentKunlin Jin
Xunming Ji
Qichuan Zhuge Editors
Bone Marrow
Stem Cell Therapy
for Stroke
Bone Marrow Stem Cell Therapy for Stroke
Kunlin Jin • Xunming Ji • Qichuan Zhuge
Editors
Bone Marrow Stem Cell
Therapy for Stroke
Editors
Kunlin Jin Xunming Ji
Department of Pharmacology Neuroscience Department of Neurosurgery, Xuanwu
University of North Texas Health Science Hospital
Center Capital Medical University
Fort Worth, TX, USA Beijing, Beijing, China
Qichuan Zhuge
Department of Neurosurgery
First Affiliated Hospital
Wenzhou Medical University
Wenzhou, China
Zhejiang Provincial Key Laboratory of
Aging and Neurological Disorder
Research
First Affiliated Hospital
Wenzhou Medical University
Wenzhou, China
ISBN 978-981-10-2928-8 ISBN 978-981-10-2929-5 (eBook)
DOI 10.1007/978-981-10-2929-5
Library of Congress Control Number: 2016959532
© Springer Nature Singapore Pte Ltd. 2017
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, express or implied, with respect to the material contained herein or for any errors
or omissions that may have been made.
Printed on acid-free paper
This Springer imprint is published by Springer Nature
The registered company is Springer Science+Business Media Singapore Pte Ltd.
The registered company address is: 152 Beach Road, #22-06/08 Gateway East, Singapore 189721,
Singapore
To our families
Preface
The book Bone Marrow Stem Cell Therapy for Stroke has been created to be the
primary resource for scientists, clinicians, teachers, students, and the public at large
in the area of cell therapy for stroke. I am honored to have had the opportunity to
edit the book with our coeditors, Qichuan Zhuge and Xunming Ji. The contributions
of the editors and editorial broad cannot be overestimated.
We know that stroke remains the fifth leading cause of death, with an incidence
of ~700,000 events per year and a prevalence of about 4.8 million individuals, of
which about 80 % are ischemic and 20 % are hemorrhagic. About one-third of these
people fail to survive the event, and of the survivors, 90 % suffer permanent deficits.
The most recent major advance in treatment, the use of thrombolytic agents to dis-
solve clots, appears to be effective only within about the first 3 hours after the initial
onset of symptoms. Widely effective treatments for stroke remain elusive, and no
effective treatment is available for chronic stroke except a lengthy program of reha-
bilitation, all the more emphasizing the need for new therapeutic developments.
Stem cell transplantation offers an exciting new therapeutic avenue for stroke,
because stem cell not only prevent damage, but also actually repair the injured
brain.
Many studies have demonstrated favorable results in animal models with various
stem cells including bone marrow-derived stem cells (BMSCs), which consequently
have resulted in several early Phase I and II clinical trials with promising outcomes.
In addition, BMSCs are easy to obtain and expand in culture; using the patient’s
own BMSCs would eliminate the risk of rejection, and BMSCs have the capacity to
migrate to the injury site, permitting systemic administration. This book reviews
recent advances in all aspects of BMSC-mediated stroke treatment in animal models
of stroke and clinical trials.
The book is organized into 14 major areas, starting with an introduction of stroke
pathophysiology and cell therapy, followed by BMSCs characterization, isolation,
culture, and identification. The third and forth chapters cover the topics of
mobilization and homing of bone marrow stem cells and interaction of BMSCs with
other cells. The next three chapters deal with the various types of BMSCs in stroke
treatment and co-transplantation strategies and combination therapies for stroke.
vii
viii Preface
The tenth section reviews the clinical studies of BMSC therapy in stroke patients.
The 11th chapter is dedicated to the area of the optimal condition of transplantation
for stroke treatment. The 12th and 13th chapters summarize the potential mecha-
nisms of transplanted cell-mediated recovery after stroke. The last section of the
book is dedicated to imaging and tracking transplanted BMSCs after stroke.
I thank our colleagues, who have contributed their expert advice to the prepara-
tion of the first book to focus on BMSC therapy for stroke. I am especially indebted
to the staff at Springer Publishing, who have been enormously helpful in moving
this book through editing and production. I hope our efforts will help to demystify
stem cell therapy for stroke for researchers and clinicians and contribute to provide
stroke patients better and more effective treatment.
Fort Worth, TX, USA Kunlin Jin
September 8, 2016
Contents
1 Ischemic Stroke Pathophysiology and Cell Therapy ........................... 1
Changhong Ren, Rongrong Han, Jingfei Shi, and Xunming Ji
2 Bone Marrow Stem Cells: Source, Characterization,
Isolation, Culture, and Identification .................................................... 37
Chengcai Zheng, Yulei Zhou, Mengxiong Pan, Siyang Lin,
Brian Wang, and Kunlin Jin
3 Mobilization and Homing of Bone Marrow Stem
Cells After Stroke .................................................................................... 55
Weikai Wang, Lefu Chen, Linhui Ruan, Kunlin Jin,
and Qichuan Zhuge
4 Interaction of Bone Marrow Stem Cells with Other Cells .................. 81
Hongxia Zhang, Shengwei Huang, Jiangnan Hu, Brian Wang,
and Kunlin Jin
5 Mesenchymal Stem Cells for Stroke Therapy ...................................... 107
Yunqian Guan, Xunming Ji, Jieli Chen, Y. Alex Zhang,
and Zhiguo Chen
6 Bone Marrow Hematopoietic Stem Cell Therapy
in Stroke ................................................................................................... 133
Michael Jiang and Ling Wei
7 Endothelial Progenitor Cell Therapy in Stroke ................................... 143
Yaying Song, Zhijun Zhang, and Guo-Yuan Yang
8 Co-transplantation Strategies and Combination
Therapies for Stroke ............................................................................... 167
Aurel Popa-Wagner, Raluca Elena Sandu, and Ovidiu Ciobanu
ix
x Contents
9 Modification of Bone Marrow Stem Cells for Homing
and Survival During Cerebral Ischemia ............................................... 201
Yaohui Tang
10 Clinical Studies of Bone Marrow-Derived Stem
Cell Therapy in Stroke Patients ............................................................. 241
Francisco Moniche, Irene Escudero, Elena Zapata,
Fernando Mancha, Ángela Vega-Salvatierra, Blanca Pardo,
and Joan Montaner
11 Bone Marrow Stem Cell Delivery Methods, Routes,
Time, Efficacy, and Safety ...................................................................... 261
Lijie Huang, Jianjing Yang, Mark Nyanzu, Felix Siaw-Debrah,
and Qichuan Zhuge
12 Potential Mechanisms of Transplanted Cell- Mediated
Recovery After Stroke............................................................................. 273
Brian Wang, Andrew Hui, and Kunlin Jin
13 Bone Marrow Stem Cell-Stimulating Factors and Brain
Recovery After Stroke............................................................................. 289
Li-Ru Zhao and Suning Ping
14 Imaging and Tracking Transplanted Bone Marrow
Stem Cells After Stroke .......................................................................... 311
Hongbin Han, Weifang Zhang, Lan Yuan, Junhao Yan,
Wei Wang, Chunyan Shi, and Yunqian Li
Contributors
Ana-Maria Buga Department of Psychiatry, University of Medicine Rostock,
Rostock, Germany
Department of Functional Sciences, Center of Clinical and Experimental Medicine,
University of Medicine and Pharmacy of Craiova, Craiova, Romania
Jieli Chen Department of Neurology, Henry Ford Hospital, Detroit, MI, USA
Lefu Chen Zhejiang Provincial Key Laboratory of Aging and Neurological
Disorder Research, First Affiliated Hospital, Wenzhou Medical University, Wenzhou
City, People’s Republic of China
Zhiguo Chen Cell Therapy Center, Xuanwu Hospital, Capital Medical University,
Beijing, China
Ovidiu Ciobanu Vivantes Humboldt-Klinikum Psyhiatrie, Psychotherapie und
Psychosomatik Zentrum für affektive Erkrankungen, Berlin, Germany
Irene Escudero Stroke Unit, Neurology Department, Instituto de Biomedicina de
Sevilla-IBiS, Hospital Universitario Virgen del Rocío, Seville, Spain
Yunqian Guan Cell Therapy Center, Xuanwu Hospital Capital Medical University,
Beijing, China
Hongbin Han Department of Radiology, Peking University Third Hospital,
Beijing, China
Beijing Key Laboratory of Magnetic Resonance Imaging Device and Technique,
Beijing, China
Rongrong Han Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical
University, Beijing, China
xi
