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The Miracle of Stem Cells ) How Adult Stem Cells are Transforming Medicine Roger J. Howe, PhD, Maynard A. Howe, PhD, Nikolai I. Tankovich, MD, PhD, David A. Howe, MD, with James R. Tager Copyright © 2011 by Stemedica Cell Technologies, Inc. Distributed by Changewell, Inc. Printed in the United States of America. All rights reserved. This book, or any parts thereof, may not be used or reproduced in any manner without written permission. For more information: Changewell, Inc., P.O. Box 7303, Rancho Sante Fe, CA 92067 www.changewell.com [email protected] T: 858-756-1491 F: 858-756-3467 ISBN 10: 0-9716250-9-3 ISBN 13: 9780971625099 Front cover: Image of cell is courtesy of Stemedica, Dr. Yuri Kudinov (MD, PhD). Design was done by Nancy Van Allen. Neural stem cell that was stained with membrane dye Dil and nuclear dye DAPI. Back cover images from left to right: Retinal Pigement Epithelial (RPE) cells image: Reprinted by permission from Macmillan Publishers Ltd: Nature Biotechnology, Osakada, F., Ikeda, H., Mandai, M., Wataya, T., Watanabe, K., Yoshimura, N., ... Takahashi, M. Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells, 26(2), 215-224, copy- right (2008). Cardiomyocyte image: Copyright (2003) National Academy of Sciences, U.S.A. Urbanek, K., Quaini, F., Giordano, T., Torella, D., Castaldo, C., Nadal-Ginard, B., ... Anversa, P. (2003). Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America, 100(18), 10440-10445. All other images on the backcover are courtesy of Stemedica, Dr. Yuri Kudinov (MD, PhD). T ABLE OF C ON T EN T S T ABLE OF C ON T EN T S PART I: A Stem Cell Primer Introduction One Family’s Story ....................................................................... 1 Chapter 1 Understanding the Promise of Stem Cells ....................................... 9 PART II: The History of Stem Cells Chapter 2 A Russian Story ............................................................................... 29 Chapter 3 From Disaster to Recovery .............................................................. 49 Chapter 4 Crests and Falls ............................................................................... 65 Chapter 5 A Quantum Leap ............................................................................ 77 PART III: The New Treatment Paradigm Chapter 6 Stroke .............................................................................................. 95 Chapter 7 Spinal Cord Injury ........................................................................ 113 Chapter 8 Traumatic Brain Injury ................................................................. 129 Chapter 9 Parkinson’s, Alzheimer’s and Other Neurological Conditions .... 141 Chapter 10 Cardiovascular Conditions ......................................................... 163 Chapter 11 Ophthalmic Conditions ............................................................. 181 Chapter 12 Wound Care ................................................................................ 195 PART IV: A Glimpse of the Future Chapter 13 Fulfilling the Promise ................................................................. 217 About Stemedica Cell Technologies, Inc. ................................................... 235 About the Authors ......................................................................................... 249 About Stemedica’s Scientific & Medical Team ........................................... 247 REFERENCES .................................................................................................. 255 INDEX ............................................................................................................. 273 A C KNOWLEDGEMEN T S ACKNOWLEDGEMENTS We are deeply indebted to the entire Stemedica team for their assistance in providing much of the clinical and laboratory science that forms the underpinnings of this book. Dr. Alex Kharazi (MD, PhD), Stemedica’s Vice President and Chief Technology Officer, and his team helped us distill a complicated science into more readily understandable text for the reader. Dr. Eugene Baranov, (PhD), Vice President of Global Research, provided much of the background for and translation of the original Russian scientific work. His efforts in coordinating interviews with many of the pioneers of stem cell research and therapy from the former Soviet Union have proved invaluable in helping us uncover the historical body of stem cell sci- ence and technology. Our consultant, Dr. Maria Alexandrova (PhD), one of the pioneers of stem cell science, shared her insights with us. Dr. Alexandrova is the daughter of Anatoly Alexandrova one of the fathers of the “Russian Manhattan” project. We also appreciate the many professional scientists and physicians from the United States, Europe and Asia that provided content, guidance and review of the various sections of the book and to the patients that shared their personal stories of successful stem cell treatments. We were also assisted by a top-level editor Dr. Mark Tager (MD) and his team comprised of Sasja Tse, Nayana Jennings, William Rodarmor and Jordan Rothenberg. Their editorial efforts, along with Nancy Van Allen and Marsha Slomowitz, who created the design, made the pages in this book come to life. Their consider- able skills are represented in every chapter. Our thanks go out to Marcie Frank for her tireless support and effort to coordinate those involved in the production of the book. We are forever grateful to Dr. Arlene Howe, whose unfortunate accident provided the inspiration for us to form Stemedica Cell Technologies, Inc. and ultimately to write this book. Last, but certainly not least, we want to express our deep appreciation and respect for our brother Dr. Ron Howe who guided the care and recovery of his wife, Arlene. His personal struggle and the invalu- able insights he learned as a caregiver demonstrated the dedication, courage and empathy required to live with and support an individ- ual suffering from a debilitating medical condition. Stemedica has integrated Ron’s important insights into the treatment protocols for patients participating in stem cell therapy. With our love and affec- tion, we dedicate this book to Arlene and Ron. Introduction: A Personal Story Introduction A Personal Story At the end of 2004, starting another company was the furthest thing from our minds. We—Roger and Maynard—were easing into retirement. Over the last three decades, we had successfully launched five companies together. At this point in our lives, non- profit ventures occupied the majority of our time, punctuated by our active involvement in competitive hockey and an occasional round of golf at the courses near our San Diego homes. We were not the only members of our family who had settled in Southern California. Our brother David, a physician, ran a thriv- ing private practice in El Cajon. Our eldest brother Ron ran a quiet bed-and-breakfast with his wife Arlene in the small town of Julian. Our brother Bruce was president of a nutraceutical company. We remained close to our sisters Mary, Janet and Gloria who lived in other locations. We spent a significant amount of time together, and as the year drew to a close, we made plans to spend Christmas with each other, as a family. When we went to sleep on December 4th, 2004, we believed that our lives had settled into a familiar rou- tine. The next day, this illusion was shattered. 1 Introduction: A Personal Story The Accident The people of Julian had not experienced a December snowstorm that strong in years. Snowflakes blanketed the roads, while furious winds made navigating the narrow winding roads almost impos- sible. It was through this storm that our sister-in-law Arlene was driv- ing her minivan. She had just picked up three workers to help clean the family’s bed-and-breakfast. On the way back home, Arlene noticed that a sharp curve loomed in the road ahead. She applied the brakes, but the build-up of ice and snow was deeper than she thought. The van suddenly went into an uncontrollable slide. In a second it had careened to the other side of the road. A brief moment later, the van was tumbling down an 80-foot ravine. When the van stopped, Arlene lay motionless, suspended in the upside-down vehicle. The three other occupants were able to escape through the window, but Arlene remained pinned, her body trapped within the twisted wreckage of the automobile’s front seat. Another motorist had witnessed the crash and quickly called 911 for assistance. Several hours later, Arlene was in the emergency unit of the nearest hospital, while doctors anxiously determined her condition. Meanwhile, Ron waited nervously for his wife to return home. After several hours had gone by, Ron called the husband of one of Arlene’s passengers, who gave him the news that sent him rushing to the hospital. Ron was soon to discover that Arlene’s condition was critical. Her spinal cord had been severely damaged and her vertebrae cracked and separated from their normal alignment. He listened, shocked Arlene Howe in the hospital. and numb, as her attending physician gave his prognosis: “If Arlene makes it, she will be a quadriplegic.” When we received the news, we rushed to be with our brother and sister-in-law at the hospital. After tearfully embracing us, Ron walked us over to Arlene’s bed. We barely recognized her. Scores of tubes, bandages, and machines surrounded her bedside.

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