Table Of ContentStem Cells in Clinical Applications
Phuc Van Pham Editor
Stem Cell Drugs - A
New Generation of
Biopharmaceuticals
Stem Cells in Clinical Applications
Series Editor
Phuc Van Pham
Laboratory of Stem Cell Research & Application
University of Science, Vietnam National University
Ho Chi Minh City, Vietnam
Stem Cells in Clinical Applications brings some of the field’s most renowned
scientists and clinicians together with emerging talents and disseminates their
cutting-edge clinical research to help shape future therapies. While each book tends
to focus on regenerative medicine for a certain organ or system (e.g. Liver, Lung and
Heart; Brain and Spinal Cord, etc.) each volume also deals with topics like the
safety of stem cell transplantation, evidence for clinical applications, including
effects and side effects, guidelines for clinical stem cell manipulation and much
more. Volumes will also discuss mesenchymal stem cell transplantation in
autoimmune disease treatment, stem cell gene therapy in pre-clinical and clinical
contexts, clinical use of stem cells in neurological degenerative disease, and best
practices for manufacturers in stem cell production. Later volumes will be devoted
to safety, ethics and regulations, stem cell banking and treatment of cancer and
genetic disease. This series provides insight not only into novel research in stem
cells but also their clinical and real-world contexts. Each book in Stem Cells in
Clinical Applications is an invaluable resource for advanced undergraduate students,
graduate students, researchers and clinicians in Stem Cells, Tissue Engineering,
Biomedical Engineering or Regenerative Medicine.
More information about this series at http://www.springer.com/series/14002
Phuc Van Pham
Editor
Stem Cell Drugs -
A New Generation
of Biopharmaceuticals
Editor
Phuc Van Pham
Laboratory of Stem Cell Research & Application
University of Science
Vietnam National University
Ho Chi Minh, Vietnam
ISSN 2365-4198 ISSN 2365-4201 (electronic)
Stem Cells in Clinical Applications
ISBN 978-3-319-99327-0 ISBN 978-3-319-99328-7 (eBook)
https://doi.org/10.1007/978-3-319-99328-7
Library of Congress Control Number: 2018958659
© Springer Nature Switzerland AG 2018
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. The publisher remains neutral with regard to jurisdictional claims
in published maps and institutional affiliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Preface
Stem cell therapy is a new therapy used in the treatment of various diseases.
Since the first transplant of a primary product of stem cells in the 1950s, s tem-
cell-based products have a long history. After more than 60 years of development,
stem-cell- based products can be grouped into six different generations, including
stem-cell- enriched fractions (first generation), pure stem cells (second
generation), long-term expanded allogeneic stem cells (third generation),
genetically modified or differentiated stem cells (fourth generation), exosomes,
extracellular vesicles, and stem cell extracts (fifth generation), and stem cells
derived from tissues or organs (sixth generation). Since the third generation,
stem-cell-based products used as drugs in the treatment of various diseases have
been referred to as stem cell drugs.
To date, stem cell drugs of the third, fourth, and fifth generations are being used
in clinics and commercially in several countries. Stem cell drugs have opened a
new age of regenerative medicine. This book focuses on stem cell drugs of the
third, fourth, and fifth generations of stem-cell-based products. In chapters 1–5, we
introduce fifth-generation stem-cell-based products containing extracellular
microvesicles obtained from stem cells. Chapters 1, 2, and 4 introduce some
applications of microvesicles as cell-based, cell-free therapy in disease treatment
and rejuvenation. Chapters 3 and 5 introduce some techniques to prepare and trigger
microvesicle production from mesenchymal stem cells. In chapters 6–8, we focus
on the third and fifth generations of stem-cell-based products. Chapter 6 introduces
the evolution of stem cell products, while chapter 7 focuses on off-the-shelf
mesenchymal stem cell technology. Chapter 8 presents some ethical and legal
issues of cord blood stem cell banks.
In preparing this book, we aimed at making it accessible to not only those
working in the field of stem cell biology, but also to nonexperts with a broad
interest in stem cells and human health. We hope the book will be of value to
all concerned with the new generation of stem-cell-based products, including
stem cell drugs.
v
vi Preface
We are indebted to the authors who graciously accepted their assignments and who
have infused the text with their energetic contributions. We are incredibly thankful to
the staff at Springer for agreeing to publish the book.
Ho Chi Minh City, Vietnam Phuc Van Pham
Contents
Part I Microvesicles
1 Using Stem Cell-Derived Microvesicles
in Regenerative Medicine: A New Paradigm
for Cell-Based-Cell-Free Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Mohammad Amin Rezvanfar, Mohammad Abdollahi,
and Fakher Rahim
2 Secretome: Pharmaceuticals for Cell-Free
Regenerative Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Nazmul Haque, Basri Johan Jeet Abdullah,
and Noor Hayaty Abu Kasim
3 Preparation of Extracellular Vesicles
from Mesenchymal Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Fernanda Ferreira Cruz, Ligia Lins de Castro,
and Patricia Rieken Macedo Rocco
4 Exosomes for Regeneration, Rejuvenation, and Repair . . . . . . . . . . . . 53
Joydeep Basu and John W. Ludlow
5 Proinflammatory Cytokines Significantly
Stimulate Extracellular Vesicle Production
by Adipose-Derived and Umbilical Cord- Derived
Mesenchymal Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Phuc Van Pham, Ngoc Bich Vu, Khanh Hong-Thien Bui,
and Liem Hieu Pham
Part II Stem Cells
6 Evolution of Stem Cell Products in Medicine:
Future of Off-the-Shelf Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Phuc Van Pham, Hoa Trong Nguyen, and Ngoc Bich Vu
vii
viii Contents
7 Off-the-Shelf Mesenchymal Stem Cell Technology . . . . . . . . . . . . . . . . 119
Ngoc Bich Vu, Phuong Thi-Bich Le, Nhat Chau Truong,
and Phuc Van Pham
8 Ethical and Legal Issues of Cord Blood Stem Cell Banking . . . . . . . . . 143
Luciana Riva, Giovanna Floridia, and Carlo Petrini
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Contributors
Mohammad Abdollahi Department of Toxicology and Diseases, Pharmaceutical
Sciences Research Center (PSRC), Tehran University of Medical Sciences (TUMS),
Tehran, Iran
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University
of Medical Sciences (TUMS), Tehran, Iran
Basri Johan Jeet Abdullah Department of Biomedical Imaging, Faculty of Medicine,
University of Malaya, Kuala Lumpur, Malaysia
Joydeep Basu Twin City Bio, LLC, Winston-Salem, NC, USA
Khanh Hong-Thien Bui University Medical Center, University of Medicine and
Pharmacy, Ho Chi Minh City, Vietnam
Ligia Lins de Castro Laboratory of Pulmonary Investigation, Carlos Chagas Filho
Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Fernanda Ferreira Cruz Laboratory of Pulmonary Investigation, Carlos Chagas
Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ,
Brazil
Giovanna Floridia Bioethics Unit, Istituto Superiore di Sanità (Italian National
Institute of Health), Rome, Italy
Nazmul Haque Department of Restorative Dentistry, Faculty of Dentistry, University
of Malaya, Kuala Lumpur, Malaysia
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA
University, Selangor, Malaysia
Noor Hayaty Abu Kasim Department of Restorative Dentistry, Faculty of Dentistry,
University of Malaya, Kuala Lumpur, Malaysia
Phuong Thi-Bich Le Van Hanh General Hospital, Ho Chi Minh City, Vietnam
John W. Ludlow Zen-Bio, Inc., Research Triangle Park, NC, USA
ix
