Artificial Cells: Biotechnology, Nanomedicine, Regenerative Medicine, Blood Substitutes, Bioencapsulation, Cell/Stem Cell Therapy (Regenerative Medicine, Artificial Cells and Nanomedicine) [1 ed.] 9789812705761, 9812705767, 9789812707789, 9812707786, 2007013738

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ARTIFICIAL CELLS

Regenerative Medicine, Artificial Cells and Nanomedicine – Vol. 1

Biotechnology,

Nanomedicine,

Regenerative Medicine,

Blood Substitutes, Bioencapsulation, and Cell/Stem Cell Therapy

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ARTIFICIAL CELLS

Regenerative Medicine, Artificial Cells and Nanomedicine – Vol. 1

Biotechnology,

Nanomedicine,

Regenerative Medicine, Blood Substitutes, Bioencapsulation,

and Cell/Stem Cell Therapy

Thomas Ming Swi Chang McGill University, Canada

World Scientific NEW JERSEY

•

LONDON

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SINGAPORE

•

BEIJING

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SHANGHAI

•

HONG KONG

•

TA I P E I

•

CHENNAI

Published by World Scientific Publishing Co. Pte. Ltd. 5 Toh Tuck Link, Singapore 596224 USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601 UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE

Library of Congress Cataloging-in-Publication Data Chang, Thomas Ming Swi. Artificial cells : biotechnology, nanomedicine, regenerative medicine, blood substitutes, bioencapsulation, cell/stem cell therapy / by Thomas Ming Swi Chang. p. ; cm. -- (Regenerative medicine, artificial cells and nanomedicine ; v. 1) Includes bibliographical references and index. ISBN-13: 978-981-270-576-1 (hardcover) -- ISBN-10: 981-270-576-7 (hardcover) ISBN-13: 978-981-270-778-9 (pbk.) -- ISBN-10: 981-270-778-6 (pbk.) 1. Artificial cells. 2. Blood substitutes.3. Nanotechnology. I. Title. II. Series. [DNLM: 1. Blood Substitutes. 2. Biotechnology. 3. Cells. 4. Nanomedicine. 5. Regenerative Medicine. WH 450 C456a 2007] RM171.7.C478 2007 615'.39—dc22 2007013738

British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library.

Copyright © 2007 by World Scientific Publishing Co. Pte. Ltd. All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the Publisher.

For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to photocopy is not required from the publisher.

Typeset by Stallion Press Email: [email protected]

Printed in Singapore.

Dedication

My wife, Lancy, for her selfless dedication, moral support and encouragement throughout my 50 years of research on artificial cells. My children, Harvey, Victor, Christine and Sandra. My grandchildren, Josh, Jared, Micaela, Matthew, Emma and Katya.

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Acknowledgements

This research would not have been possible without access to the vast amount of the scientific knowledge gathered by numerous investigators throughout the centuries around the world. More immediately, there are many people who have at one time or another given invaluable encouragement, support or advice. It is not possible to acknowledge all, except to mention a few early examples when this work was at its very beginning. Sir Arnold Burgen, F.R.S., while at McGill, has through his teaching and discussions initiated my deep interest in the area of membrane and cell physiology. In 1956, he supported my request to Professor F. C. MacIntosh, F.R.S., then Chairman of the Department of Physiology, to move my research from my dormitory room to a corner of the teaching laboratory in the department. Professor MacIntosh has, in addition, given me much encouragement and support at the beginning. In 1962, Professor S. G. Mason, was interested in using my 1957 artificial cells for some of his rheology experiments and invited me to his laboratory for six months. I am thankful to the Canadian biomedical scientists for their open enthusiasm and standing ovation when I first presented this study at the Annual Conference of the Canadian Federation of Biological Societies in 1963. This and the acceptance of my paper as the sole author by Science in 1964, suggested to me that this research might have some future potential for use in medicine. This played an important role in my decision to continue with the research rather than to go into clinical practice. Professor D. V. Bates, then Chairman of the Department of Physiology, for his support and help in greatly expanding my research facilities. Professor J. Beck, Physician-in-Chief of the RoyalVictoria Hospital, for his support in my first clinical trials on vii

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hemoperfusion and the nephrologists at the McGill Teaching hospitals for referring their patients to me to carry out the hemoperfusion procedures — especially Dr. A. Gonda, Dr. Paul Barre, Dr. M. Levy, and Dr. J Dirks. My uncle, Professor Robert SM Chang, especially for his advice on academic “protocols.” Professor S. Freedman, while dean of medicine, recognized this research effort as the Artificial Cells and Organs Research Centre at McGill University. My sincere appreciation also goes to Professor W. Kolff, Professor A. Burton, Professor O. Denstedt, and many others for their interests, encouragement, and support especially in the early phase of this research. This included professors, chairmen of departments, deans of faculties, vice-principals and principals at McGill University and the many colleagues around the world. This research would not have been possible without my wife, Lancy. Through her cheerful acceptance she has made it possible for me to combine this research with the heavy load of a medical student in the early years. Since 1958, in addition to her moral support, she has looked after everything for me at home and even in my office so as to allow me to concentrate completely and fully on my research and other academic activities. She has also contributed extensively to this monograph by carrying out the very time consuming and laborious task of inputting, typing, arranging and editing the very large reference section. It has been a pleasure to work in my laboratory with the many past and present graduate students, research fellows, research assistants, research associates and others, especially (alphabetically): Barre, P, Bourget, L, Bruni, S, Cameron, D, Campbell J, Cattaneo, M, Chang, H, Chang, V, Chawla, AS, Chirito, E, Chow, KM, Chuang, S, Coffey, JF, Cole, C, Coromili, V, Cousineau, J, D’Agnillo, F, Daka, J, Dixit, V, Ergan, F, Espinosa-Melendez, E, Francoeur, TE, Fustier, C, Garofalo, F, Grunwald, J, Grunwald, J, Gu, JS, Gu, KF, Hertzman, CM, Hewish, M, Holeczek, K, Ilan, E, Ito, Y, Johnson, L, Kashani, SA, Keipert, PE, Khanna, R, Kuntarian, N, Kuruvilla, S, Lee Burns, T, Lesser, B, Lister, C, Liu, ZC, Lloyd-George, I, Lo, KS, Malave, N, Malouf, C, Migchelsen, M, Mobed, M, Mohsini, K, Morley, D, Morton, P, Nalchesky, P, Nasielski, P, Ning, J, Nishiya, T, O’Keefe, P, Piskin, E, Pont, A, Powanda, D,

Acknowledgements

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Poznansky, M, Prakash, S, Prichard, S, Quebec, EA, Ransome, O, Razack, S, Reiter, B, Resurreccion, ´ E, Rodrigue, A, Rong, J, Rosenthal, AM, Safos, S, Sarkissian, CN, Shi, ZQ, Shu, CD, Sipehia, R, Siu-Chong, E, Sorrini, P, Stark, A, Stefanescu, A, Tabata, Y, Tani, T, Taroy, E, Varma, R, Verzosa, A, Wahl, HP, Walter, S, Watson W, Wong, H, Wong, N, Yu, BL, Yu, WP, Yu, YT, Yuan, ZY, Zheng, WH, Zhou, MX, Zolotareva, E and others. I gratefully acknowledge the financial support as follows: My parents in the first summer of 1957. The Faculty of Medicine at McGill for support throughout the next three summers. When this research was carried out on a full time basis from 1962, the Medical Research Council of Canada for the research support and for the awards, respectively, as Medical Research Fellow (1962–1965), Medical Research Council Scholar (1965–1968), and MRC Career Investigator from 1968 until the end of the career investigator program in 1999. After the MRC became the new Canadian Institutes of Health Research, it continued with ongoing research supports. When the Quebec Ministry of Education, Science and Technology started the new “Virage Centre of Excellence in High Technology” program, they awarded me one of the first centers. The Bayer/Canadian Red Cross Society/Medical Research Council of Canada Joint Funds program had supported my research on blood substitutes even before the H.I.V. crisis in donor blood. The more recent Quebec Ministry of Health’s Hemovigillance and Transfusion Medicine Program has awarded me its first Research Group (d’equipe) to work on “Biomedical Research on Blood Substitutes in Transfusion Medicine.” In addition to the above major long-term research supports, there were also smaller and shorter term research supports from other agencies and organizations over the last many years. It has been a pleasure to accept the invitation of World Scientific Publishing to prepare this monograph. Their scientific editor, Ms. SC Lim, has been most helpful throughout the preparation of this monograph.

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Contents

Dedication

v

Acknowledgements

vii

Chapter 1. 50th Anniversary of Artificial Cells

1

1.1. 1.2. 1.3.

1 2

1.4. 1.5.

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . Starting with Artificial Red Blood Cells . . . . . . . . . . . . . Further Research and the First Routine Clinical Use of Artificial Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Importance of Progress in Parallel Areas of Biotechnology, Molecular Biology, and Regenerative Medicine . . . . . . . . Historical Milestones . . . . . . . . . . . . . . . . . . . . . . .

5 7 7

Chapter 2. Basic Principles

12

2.1.

12 12

2.2.

Basic Features of Artificial Cells . . . . . . . . . . . . . . . . . Basic features of early artificial cells . . . . . . . . . . . . . . . Present status of the basic features of artificial cells of macro, micron, nano and molecular dimensions . . . . . . . . . Nanotechnology and Nanobiotechnology . . . . . . . . . . . . Nanobiotechnology and artificial cells . . . . . . . . . . . . . . Nanobiotechnology and the assembling of hemoglobin with enzymes that remove oxygen radicals . . . . . . . . Nanobiotechnology for the assembling of hemoglobin with other enzymes . . . . . . . . . . . . . . . . . . . . . xi

14 15 15 17 17

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Conjugation of polymer with proteins . . . . . . . . . . . . . . 2.3. Cell Homogenate, Organelle, Enzymes and Multienzyme Systems . . . . . . . . . . . . . . . . . . . . . . Cell homogenate . . . . . . . . . . . . . . . . . . . . . . . . . Enzymes and enzyme therapy . . . . . . . . . . . . . . . . . . Multienzyme systems with cofactor recycling . . . . . . . . . . 2.4. Artificial Cells Containing Intracelluar Compartments . . . . . 2.5. Artificial Cells Containing Biologics and Magnetic Material . . 2.6. Cells, Islets, Stem Cells, Genetically-engineered Cells and Microorganisms . . . . . . . . . . . . . . . . . . . . . . . . . Artificial cells containing cells . . . . . . . . . . . . . . . . . . Stem cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Genetically-engineered cells . . . . . . . . . . . . . . . . . . . 2.7. Artificial Cells Containing Bioadsorbents . . . . . . . . . . . . 2.8. Research on Membrane Model Systems . . . . . . . . . . . . . 2.9. Cell Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . 2.10. Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . Polymeric semipermeable microcapsules . . . . . . . . . . . . Biodegradable polymeric artificial cells, nanoparticles, nanocapsules . . . . . . . . . . . . . . . . . . . . . . . . Liposomes — lipid membrane artificial cells . . . . . . . . . . 2.11. Other Systems . . . . . . . . . . . . . . . . . . . . . . . . . . .

18 18 18 19 20 21 22 22 22 24 24 25 27 28 28 28 29 29 30

Chapter 3. Oxygen Carriers Based on Nanobiotechnology

31

3.1. 3.2. 3.3.

31 32 32 33 34 35 35 35 36

3.4. 3.5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hemoglobin as Oxygen Carrier . . . . . . . . . . . . . . . . . Modified Hb . . . . . . . . . . . . . . . . . . . . . . . . . . . . PolyHb based on nanobiotechnology (Fig. 3.1) . . . . . . . . . Conjugated Hb (Fig. 3.1) . . . . . . . . . . . . . . . . . . . . . Intramolecularly crosslinked single tetrameric Hb (Fig. 3.1) . . Recombinant human Hb (Fig. 3.1) . . . . . . . . . . . . . . . . Present status . . . . . . . . . . . . . . . . . . . . . . . . . . . PolyHb in Clinical Trials . . . . . . . . . . . . . . . . . . . . . Nanobiotechnology-based PolyHb Compared with other Modified Hb . . . . . . . . . . . . . . . . . . . . . . . . . . . Vasopressor effects . . . . . . . . . . . . . . . . . . . . . . . .

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Theories why vasopressor effects are observed only in some types of modified Hb? . . . . . . . . . . . . . . . . . . . . Effects of tetrameric Hb on vasoactivity and ECG . . . . . . . . 3.6. PolyHb with