Stem Cells

A Short Course

Rob Burgess

• Publisher: Wiley-Blackwell
• Year: 2015
• Print ISBN: 9781118439197
• eBook ISBN: 9781118439173
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Cell Biology
• Index: Biological Sciences

Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem cells in drug discovery and therapeutic applications in spinal cord injury, brain damage, neurological and autoimmune disorders, among others.

Written by a leader in the field, Stem Cells: A Short Course appeals to both students and instructors alike, appealing to academic enthusiasm for stem cell research and applications.

Chapter 1
A HISTORY OF STEM CELL RESEARCH

Chapter 1 outlines and describes the maturation of stem cell research, from early contemplations on the power of cell fate to cutting-edge clinical trials involving human embryonic stem cell (hESCs). A multitude of different stem cell types are described as they make their chronological appearance on the research front and key researchers as well as their findings and discoveries are highlighted throughout the chapter.

“The possibility of obtaining a strain of cells in tissue culture which may become determined to differentiate in a variety of alternative ways is very attractive.”

Martin Evans, PhD (1972)—2007 Nobel Prize Winner in Physiology or Medicine

EARLY STUDIES

The existence of stem cells, which are defined as biological cells capable of self-renewal and the capacity to differentiate into a variety of cell types and are present within most if not all multicell organisms, has been contemplated for greater than 100 years. In fact, the concept of “stemness” can be traced back as far as ∼300 BC when Aristotle disagreed with the generationally accepted hypothesis of spontaneous generation (Figure 1.1).

Figure 1.1 Timeline of historical advances in stem cell theory and research. (Adapted from Rob Burgess, Stem Cells Handbook (Humana Press), 2nd Edition, Chapter 1.)

Russian-born medical doctor Alexander A. Maximow first coined the term “stem cell” in 1908, while addressing a hematologic society congress in Berlin (see Focus Box 1.1). Maximow was a scientist and histologist who spent several years around the turn of the 20th century contemplating the existence of a unique cell type that would allow for generation of many differentiated, mature phenotypes. Maximow’s main focus was on blood cell type identity and what drives the generation of the terminally differentiated cells in the hematopoietic system. It was as a professor at the Imperial Military Academy in Saint Petersburg, Russia from 1903 to 1922, where he refined his theories on the existence of a common hematopoietic precursor cell. He is generally credited with the formulation of the theory of hematopoiesis, which states that all blood cellular components are derived from a common precursor stem cell. Maximow finished his career as a professor of anatomy at the University of Chicago.

After the initial contemplation of the existence of hematopoietic stem cells (HSCs) in 1908, the field was relatively silent for more than 50 years. It was not until the early sixties when true scientific advancements in the area of stem cell research began to take place. Specifically, in 1963 researchers Ernest McCulloch and James Till (Altman and Das, 1967) of the University of Toronto demonstrated the existence of stem cells in the bone marrow (Figure 1.2). This was accomplished by injecting bone marrow cells into irradiated immune-deficient mice, which resulted in the growth of visible lumps termed spleen colonies. It was postulated that these colonies were the result of bone marrow-derived stem cells, and their clonal origin was confirmed. Published in the journal Nature that year, this finding is considered to be one of the most seminal discoveries in the field of stem cell research, laying the groundwork for virtually every major breakthrough in the discipline since.

Figure 1.2 The late Ernest McCulloch and James Till after accepting the 2005 Lasker Award for their studies on bone marrow-derived stem cells. Ernest McCulloch is at left. (Photograph courtesy Environmental Protection Agency; reprinted with permission.)

---

Focus Box 1.1: Alexander A. Maximow and the Theory of Stem Cells

Alexander A. Maximow (1874–1928) was a Russian-born medical doctor and histologist and the first person to contemplate the existence of stem cells. His “theory of hematopoiesis” and histological textbook, which has been suggested to be the world’s most respected textbook in histology, laid the groundwork for many of the stem cell discoveries impacting medicine today. (Photo courtesy Wikimedia Commons; reprinted with permission.)

---

The lymphatic system was not the only area of hot pursuit for the identification and characterization of stem cells. In 1967, a key demonstration of neurogenesis, defined as the generation of neurons and glial cells, occurring in the adult brain was accomplished by Drs. Joseph Altman and Gopal Das of Massachusetts Institute of Technology (Prindull et al., 1978) (Figure 1.3). In these studies, an autoradiographic technique was employed to measure both mitotic activity and tag cells for tracking at later time points. To accomplish this, tritiated (³H) thymidine was injected intraperitonially into 6-day-old guinea pigs and then monitored for incorporation into the cells of the cerebellar external germinal and cortical subependymal layers of the brain. Tritiated thymidine will incorporate into the DNA of mitotically active cells, thus marking cell division. In addition, it will remain in these cells long term as a tag for subsequent cell marking and characterization. Dr. Altman’s group used this technique to reveal active mitosis in the brains of adult guinea pigs followed by confirmation that the tagged cells differentiate into identifiable small-caliber mature interneurons he termed “microneurons. ” The findings of Altman and Das went against the no new neurons central dogma of leading neuroscientist Santiago Ramon y Cajal, and thus were largely dismissed by the scientific community (Altman and Das, 1967). It was only in the 1990s when adult neurogenesis was “rediscovered” that Altman’s theories on adult brain neurogenesis were accepted by the scientific community. Dr. Altman and his wife and colleague, researcher Shirley Altman-Bayer, still actively promote their research theories today and have a forthcoming book titled MENTAL EVOLUTION: Origins of the Human Body, Brain, Behavior, Consciousness, and Culture.

Figure 1.3 Discovery of active neurogenesis in the adult brain. The arrows denote ³H-thymidine uptake in glial cells in rodent brain regions associated with trauma. Neurons and neuroblasts also demonstrated some staining, confirming mitosis and corresponding neurogenesis. (Photo courtesy Nature (Altman and Das, 1967); reprinted with permission.)

In 1968, a major therapeutic breakthrough based on the potential of stem cells present in bone marrow was realized when the first successful human bone marrow transplant was accomplished by the late American physician Dr. Robert Alan Goode while he was Professor in Pediatrics, Microbiology, and Pathology at the University of Minnesota Medical School (Figure 1.4). The transplant was performed between siblings for the treatment of severe combined immunodef...

Table of contents

• Cover
• Title page
• Copyright
• Dedication
• PREFACE TO THE PROFESSOR
• PREFACE TO THE STUDENT
• ACKNOWLEDGMENTS
• LIST OF CASE STUDIES
• LIST OF FOCUS BOXES
• CHAPTER 1 A HISTORY OF STEM CELL RESEARCH
• CHAPTER 2 FUNDAMENTALS OF STEM CELLS
• CHAPTER 3 EMBRYONIC STEM, FETAL, AND AMNIOTIC STEM CELLS
• CHAPTER 4 ADULT STEM CELLS
• CHAPTER 5 NUCLEAR REPROGRAMMING
• CHAPTER 6 CANCER STEM CELLS
• CHAPTER 7 STEM CELLS AS DRUG DISCOVERY PLATFORMS
• CHAPTER 8 THERAPEUTIC APPLICATIONS OF 
STEM CELLS
• ABOUT THE AUTHOR
• INDEX
• EULA