The second edition of Stem Cells: Scientific Facts and Fiction provides the non-stem cell expert with an understandable review of the history, current state of affairs, and facts and fiction of the promises of stem cells. Building on success of its award-winning preceding edition, the second edition features new chapters on embryonic and iPS cells and stem cells in veterinary science and medicine. It contains major revisions on cancer stem cells to include new culture models, additional interviews with leaders in progenitor cells, engineered eye tissue, and xeno organs from stem cells, as well as new information on 'organs on chips' and adult progenitor cells.
In the past decades our understanding of stem cell biology has increased tremendously. Many types of stem cells have been discovered in tissues that everyone presumed were unable to regenerate in adults, the heart and the brain in particular. There is vast interest in stem cells from biologists and clinicians who see the potential for regenerative medicine and future treatments for chronic diseases like Parkinson's, diabetes, and spinal cord lesions, based on the use of stem cells; and from entrepreneurs in biotechnology who expect new commercial applications ranging from drug discovery to transplantation therapies.
- Explains in straightforward, non-specialist language the basic biology of stem cells and their applications in modern medicine and future therapy
- Includes extensive coverage of adult and embryonic stem cells both historically and in contemporary practice
- Richly illustrated to assist in understanding how research is done and the current hurdles to clinical practice
The second edition of Stem Cells: Scientific Facts and Fiction provides the non-stem cell expert with an understandable review of the history, current state of affairs, and facts and fiction of the promises of stem cells. Building on success of its award-winning preceding edition, the second edition features new chapters on embryonic and iPS cells and stem cells in veterinary science and medicine. It contains major revisions on cancer stem cells to include new culture models, additional interviews with leaders in progenitor cells, engineered eye tissue, and xeno organs from stem cells, as well as new information on "e;organs on chips"e; and adult progenitor cells. In the past decades our understanding of stem cell biology has increased tremendously. Many types of stem cells have been discovered in tissues that everyone presumed were unable to regenerate in adults, the heart and the brain in particular. There is vast interest in stem cells from biologists and clinicians who see the potential for regenerative medicine and future treatments for chronic diseases like Parkinson's, diabetes, and spinal cord lesions, based on the use of stem cells; and from entrepreneurs in biotechnology who expect new commercial applications ranging from drug discovery to transplantation therapies. Explains in straightforward, non-specialist language the basic biology of stem cells and their applications in modern medicine and future therapy Includes extensive coverage of adult and embryonic stem cells both historically and in contemporary practice Richly illustrated to assist in understanding how research is done and the current hurdles to clinical practice
Front Cover 1
Stem Cells: Scientific Facts and Fiction 4
Copyright Page 5
Contents 6
Preface 10
Acknowledgements 12
1 The Biology of the Cell 14
1.1 Organisms’ Composition 15
1.2 Deoxyribonucleic Acid, Genes, and Chromosomes 17
1.3 How the Amount of Messenger Ribonucleic Acid is Regulated 24
1.4 From Messenger Ribonucleic Acid to a Functional Protein 27
1.5 From Deoxyribonucleic Acid and Proteins to a Cell with a Specific Function 28
1.5.1 Epigenetic Regulation 30
1.5.2 Ribonucleic Acid Interference 33
1.6 Deoxyribonucleic Acid Differences Between Genomes 33
1.7 Diseases Due to Variations and Genome Mutations 34
1.8 Dominant or Recessive 35
1.9 Deoxyribonucleic Acid Outside the Nucleus: Bacterial Remains 35
1.10 Cell Lines and Cell Culture 40
2 Embryonic Development 46
2.1 Fertilization and Early Embryo Development 56
2.2 Sex Cells and Germ Cell Tumors 63
3 What Are Stem Cells? 66
3.1 What are the Properties of Stem Cells That Make Them Different from Other Cells? 67
3.2 Totipotency and Pluripotency, and Embryonic Stem Cells 70
3.3 Multipotency, Unipotency, and Adult Stem Cells 75
3.4 Cell Division and Aging: The Role of Telomerase 76
3.5 The Relationship Between Cell Division and Differentiation: Epigenetics 76
3.6 Epigenetics in Stem Cells 79
4 Of Mice and Men: The History of Embryonic Stem Cells 82
4.1 How it All Began: Pluripotent Cells in Early Embryos 83
4.2 Mouse Embryonal Carcinoma Cell Lines 86
4.3 Pluripotent Cells in an Early Embryo 90
4.4 Mouse Embryonic Stem Cell Lines 92
4.5 Toward Human Embryonic Stem Cells 96
4.6 On the Road to Stem Cell Therapy 103
4.7 Biased Interpretation 105
4.8 The Future: Stem Cell Transplantation as a Clinical Treatment 106
4.9 Breakthrough of the Decade in the Twenty-First Century: Induced Pluripotent Stem Cells 107
5 Origins and Types of Stem Cells: What’s in a Name? 114
5.1 Pluripotent Stem Cells 115
5.1.1 Embryonal Carcinoma Cells 115
5.1.2 Embryonic Stem Cells 117
5.1.3 Embryonic Germ Cells 124
5.1.4 Spermatogonial Stem Cells 128
5.1.5 Induced Pluripotent Stem Cells 132
5.2 Multipotent Stem Cells 134
5.2.1 Bone Marrow 136
5.2.2 Umbilical Cord Blood 138
6 Cloning: History and Current Applications 144
6.1 Before Dolly 145
6.2 Cloning Pets: Snuppy, Missy, and Copycat 161
6.3 Just Imagine What Could Be 165
6.4 Cloning Domestic Livestock 170
6.5 Cloning Challenges 171
7 Regenerative Medicine: Clinical Applications of Stem Cells 176
7.1 Therapeutic Cell Transplantation 182
7.2 Number of Cells Needed for Cell Transplantation 185
7.3 Why Some Diseases will be Treatable with Stem Cells in the Future and Others Not 187
7.3.1 Loss of One Cell Type or More Cell Types 189
7.3.2 Inherited and Acquired Diseases 191
7.3.3 Diabetes Type 1: An Autoimmune Disease 193
7.3.4 Spinal Cord Injury and Multiple Sclerosis: Restoring Demyelination 195
7.3.5 Macular Degeneration: The Ideal Disease 197
7.3.6 Deafness 199
7.4 The Best Stem Cells for Transplantation 202
7.5 Combining Gene Therapy with Stem Cell Transplantation 206
7.6 Where to Transplant Stem Cells and Their Effect 209
7.7 Cell Types Available for Cell Transplantation 214
7.7.1 Adult Stem Cells 214
7.7.2 Embryonic and Induced Pluripotent Stem Cells 216
7.8 Transplantation of Stem Cells: Where We Stand 219
7.9 Risks Associated with a Stem Cell Transplantation 224
7.10 Stem Cells Rejected After Transplantation 227
7.10.1 How the Body’s Immune System Recognizes a Cell as Foreign 228
7.10.2 Reverse Rejection: Graft-Versus-Host 231
7.10.3 How to Prevent Rejection of a Cell Transplant 234
7.11 Tissue Engineering 239
8 Stem Cells in Veterinary Medicine 248
8.1 Treatment of Family Pets 250
8.1.1 Tendon in the Horse 251
8.1.2 Osteoarthritis in Dogs 254
8.1.3 Induced Pluripotent Stem Cells 257
9 Cardiomyocytes from Stem Cells: What Can We Do with Them? 260
9.1 The Heart and Cardiac Repair 264
9.2 From Pluripotent Stem Cells to Cardiomyocytes 276
10 Adult Stem Cells: Generation of Self-Organizing Mini-Organs in a Dish 292
10.1 Adult Stem Cells in Internal Organs 293
10.2 Adult Stem Cells in the Intestine 296
10.3 Adult Stem Cells in Muscle Tissue 299
10.4 What We Have Learnt About Adult Stem Cells 301
10.5 The Future: Organoids to Repair Tissues and Organs 302
11 Stem Cell Tourism 304
11.1 Definition of Stem Cell Tourism 305
11.2 What's the Difference Between Trials and Treatment? 311
11.3 Perspective of the International Society for Stem Cell Research 326
12 Cancer Stem Cells: Where Do They Come From and Where Are They Going? 328
12.1 Cancer: Observations and Questions 329
12.2 Introduction to Stem Cells and Cancer 330
12.2.1 A Brief History of Cancer Stem Cells 331
12.3 The Behavior of Cancer Cells: Not All Tumors and Not All Cells Within a Tumor Look the Same 334
12.3.1 A Darwinian View: Evolution of a Tumor 335
12.4 Colon Adenoma: A Case in Point for the Role of an Adult Stem Cell as the Stem Cell of Origin 336
12.4.1 Development of a Colon Adenoma 336
12.4.2 When Does a Tumor Become Malignant and Metastasize to Different Organs? 339
12.4.3 Interaction between Cancer Cells and Their Environment Leads to Phenotypic Heterogeneity 340
12.5 How to Become a Cancer Stem Cell: Epithelial Mesenchymal Transition 347
12.6 How Developmental Signal Transduction Pathways Become Active in Cancer Cells 348
12.7 Cancer Stem Cells as Circulating Tumor Cells 350
12.8 The Final Step: Initiation of Metastatic Growth 350
12.9 A Cancer Stem Cell: Can it Differentiate to Another Cell Type? 351
12.10 Cancer Stem Cells: Development of New Drugs to Treat Cancer 352
12.11 Conclusions and Research Challenges 354
13 Human Stem Cells for Organs-on-Chips: Clinical Trials Without Patients? 356
13.1 Introduction 357
13.2 Organs-on-Chips 358
13.3 Why We Need Human Organ and Disease-on-Chip Models 361
13.4 Human Organ-on-a-Chip Models for Certain Diseases 364
13.5 Human Disease Models as Organs-on-Chips: Challenges 365
13.6 Where We are Now with Organ-on-a-Chip Technology 365
13.6.1 Pluripotent or Adult Stem Cells 368
13.6.2 Organ-on-a-Chip Technology to Mediate Formation of Functional Tissues and Organs 369
13.7 Applications of Organs-on-Chips 371
13.7.1 Model Systems for Drug Toxicity Screening 372
13.7.2 Human Disease Models for Drug Target Discovery and Drug Development: A Role for Organs-on-Chips 372
13.8 Conclusion 373
14 Stem Cells for Discovery of Effective and Safe New Drugs 376
14.1 Drug Discovery: A Short Historical Perspective 377
14.2 Modern Drug Discovery 380
14.3 Challenges and Opportunities in Drug Discovery 382
14.4 How the Safety of New Drugs is Secured 388
Acknowledgments 390
15 Patents, Opportunities, and Challenges: Legal and Intellectual Property Issues Associated with Stem Cells 394
15.1 Companies and Alliances 397
15.2 Patent Issues: Current Intellectual Property Landscape 398
15.2.1 Wisconsin Alumni Research Foundation 399
15.3 Europe Versus the United States 400
15.4 More Legal and Ethical Issues 406
15.4.1 Privacy and Ownership 407
Acknowledgments 408
Further Reading 408
16 Stem Cell Perspectives: A Vision of the Future 410
16.1 Combining Technologies: New Human Disease Models for Drug Discovery 415
16.2 Personalized Medicine and Safer Drugs 417
16.3 Final Note 419
Glossary 422
Index 430
Photo Credits 440
The Biology of the Cell
This book is about stem cells. Stem cells and their applications in clinical medicine, biotechnology, and drug development for pharmaceutical companies involve many facets of biology, from genetics, epigenetics, and biochemistry to synthetic scaffolds and three-dimensional architecture for tissue engineering. For this reason, the most important molecular and cell biological principles that are needed to understand stem cells will be introduced to the reader in this chapter.
Keywords
cell; DNA; RNA; protein; transcription; translation; genetic code; amino acid
Outline
1.2 Deoxyribonucleic Acid, Genes, and Chromosomes 4
1.3 How the Amount of Messenger Ribonucleic Acid is Regulated 11
1.4 From Messenger Ribonucleic Acid to a Functional Protein 14
1.5 From Deoxyribonucleic Acid and Proteins to a Cell with a Specific Function 15
1.5.1 Epigenetic Regulation 17
1.5.2 Ribonucleic Acid Interference 20
1.6 Deoxyribonucleic Acid Differences Between Genomes 20
1.7 Diseases Due to Variations and Genome Mutations 21
1.9 Deoxyribonucleic Acid Outside the Nucleus: Bacterial Remains 22
This book is about stem cells. Stem cells and their applications in clinical medicine, biotechnology, and drug development for pharmaceutical companies involve many facets of biology, from genetics, epigenetics, and biochemistry to synthetic scaffolds and three-dimensional architecture for tissue engineering. For this reason, the most important molecular and cell biological principles needed to understand stem cells will be introduced to the reader in this chapter.
1.1 Organisms’ Composition
Humans and animals, as well as plants and trees, contain many different functional organs and tissues. These, in turn, are composed of a large variety of cells. Cells are therefore the basic building blocks that make up the organism. All animal cells have a similar structure: (1) an outer layer called the plasma membrane, which is made up of a double layer of lipid molecules, and (2) an inner fluid known as cytoplasm. The cytoplasm contains a variety of small structures called organelles, each of which has a specific and essential function within the cell. Most cell organelles are themselves separated from the cytoplasm by their own membrane. The shape of the cell is determined and supported by the cytoskeleton, a flexible scaffolding composed of polymers of protein molecules which form a network that shapes the cell and allows it to move and “walk.” Inside the cell, countless proteins facilitate the chemical and physical reactions and transport of other molecules required for carrying out specific cellular functions (Figure 1.1).
Figure 1.1 Schematic representation of an animal cell. The cell contains a fluid called the cytoplasm, enclosed by a cell (or plasma) membrane. The nucleus contains the genetic information; the DNA. The shape of a cell is determined by its cytoskeleton. Proteins and lipids are generated and assembled in the endoplasmic reticulum. The Golgi apparatus is then responsible for further transport within the cell. Lysosomes are small vesicles with enzymes that can break down cellular structures and proteins that are no longer required. The energy necessary for the cell is generated by the mitochondria. Source: Stamcellen Veen Magazines.
The most prominent organelle when a cell is viewed under the microscope is the nucleus. This contains the chromosomes, which are in part made up of deoxyribonucleic acid (DNA)—one long molecule of DNA per chromosome—representing the organism’s “blueprint” for what it is and what it does. Although cells can have different shapes and functions, the DNA sequence in all cells of one individual is, in principle, identical (with the exception of certain blood cells). Other prominent structures in the cell are the mitochondria. These organelles are present in large numbers and generate the energy required by the cell. Cells with very large energy requirements, such as heart cells, contain correspondingly higher numbers of mitochondria. Energy is also required for the formation of proteins using the genetic code as a template. Rudimental proteins made in this way are delivered to the tubular structures of the endoplasmic reticulum, where they are processed into actual working proteins in yet another organelle, the Golgi apparatus. They are then transported in small vesicles, termed vacuoles, to the site in the cell where they are required for their own specific function. Each cell is, thus, a highly dynamic structure with its own powerhouse, factories, and transport systems.
1.2 Deoxyribonucleic Acid, Genes, and Chromosomes
The deoxyribonucleic acid (DNA) in each cell of our body contains all of the information needed to create a complete individual. In humans, DNA is divided into around 23,000 different genes, each of which encodes the blueprint for one or more proteins. What does the information in the DNA look like, and how is it translated into the production of proteins? How does the cell decide which proteins to make? This together determines what stem cells can (or cannot) do and is important for understanding what stem cells can mean for medical research and biotechnology (Figure 1.2).
Figure 1.2 DNA can be isolated from cells and precipitated (separated from liquid). It then appears as a white, glue-like substance. Source: Stamcellen Veen Magazines.
A DNA strand is composed of a long series of nucleotides. Each nucleotide consists of a deoxyribose molecule, which forms the backbone of the DNA molecule, and is linked to one of four bases: adenine (A), guanine (G), thymine (T), or cytosine (C). Nucleotides are connected by phosphate groups (molecules containing the element phosphor) and, as a result, form a long chain. The specific order (or sequence) of the different bases represents the core of the DNA code that contains the blueprint of an organism. The DNA sequence is therefore usually written as a series of the letters A, G, C, and T, just as letters in a book. Two single strands of DNA combine to form a double-stranded DNA molecule as complementary bases form base pairs held together through hydrogen bridges (or links): adenine binds to thymine, while guanine always binds to cytosine (Figure 1.3). The two strands are therefore complementary; when the sequence of one strand is known, the sequence of the other strand is also known. If, for example, part of one strand is AGTATTC, the other strand would read TCATAAG. The information in the nucleus can be compared to a library, with the genes represented as books and the nuclear code represented by letters in the books.
Figure 1.3 A single DNA strand is a long polymer composed of sugar (deoxyribose) and phosphate groups that together form the backbone of the DNA. Any one of the possible four bases—adenine, thymine, cytosine, or guanine—is coupled to the deoxyribose strand. Source: Stamcellen Veen Magazines.
Normally, the DNA in a cell nucleus is double stranded and forms a long chain (Figure 1.4). These long, double-stranded DNA molecules (one DNA molecule can be up to 10 cm long) form the famous Watson and Crick DNA “double helix” structure, itself wrapped around a core of a special family of proteins called histones (Figure 1.5). If all of the DNA in one cell was unrolled it would be about 2 m long. This means that in an adult person made up of ~1013 cells, the total length of the DNA is an astonishing 2×1013 m. For comparison, this is equivalent to going ~500,000,000 times around the world (Figure 1.6).
Figure 1.4 A complete DNA molecule is composed of two strands that are coupled by hydrogen bonds. Adenine is always coupled to thymine; guanine is always coupled to cytosine. Source: Stamcellen Veen Magazines.
Figure 1.5 When two DNA strands are bound together they form a double helix structure, with bases (orange, red, green, purple) on the inside of the helix and the sugar-phosphate backbone (blue) on the outside.
Figure 1.6 James Watson (here with Anja van de Stolpe, one of the authors), who, with Francis Crick, unraveled the molecular structure of DNA. The pair discovered that DNA forms a double helix, in which complementary bases are coupled through hydrogen bonds. Source: Anja van de Stolpe.
Histone proteins provide an extremely long DNA molecule with the support and guidance to fold into a complicated three-dimensional form that fits into the nucleus. This intricate combination of DNA and proteins is called chromatin, and each long DNA strand folded around proteins called a chromosome. The ends of the DNA molecules that form the caps of the chromosomes are called telomeres. These telomeres protect the chromosome ends from DNA damage but are shortened after each cell division (Figure 1.7). Cells can continue dividing until the telomeres are “used up;” this is...
| Erscheint lt. Verlag | 23.5.2014 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie |
| Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie | |
| Naturwissenschaften ► Biologie ► Zellbiologie | |
| ISBN-10 | 0-12-411567-5 / 0124115675 |
| ISBN-13 | 978-0-12-411567-5 / 9780124115675 |
| Haben Sie eine Frage zum Produkt? |
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