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Anaerobiosis and Stemness - 1st Edition - ISBN: 9780128005408, 9780128006115

Anaerobiosis and Stemness

1st Edition

An Evolutionary Paradigm for Therapeutic Applications

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Authors: Zoran Ivanovic Marija Vlaski-Lafarge
Hardcover ISBN: 9780128005408
eBook ISBN: 9780128006115
Imprint: Academic Press
Published Date: 1st November 2015
Page Count: 326
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Anaerobiosis and Stemness: An evolutionary paradigm provides a context for understanding the many complexities and evolutionary features of stem cells and the clinical implications of anaerobiosis stem cells.  Combining theoretical and experimental knowledge, the authors provide a broad understanding of how the absence or low concentration of oxygen can play an influential role in the maintenance and self-renewal of stem cells and stem cell differentiation.  This understanding has clinical implications for the fields of regenerative medicine, cancer biology and transplantation, as well as cell engineering and cell therapy. Anaerobiosis and Stemness is an important resource for stem cell and developmental biologists alike, as well as oncologists, cancer biologists, and researchers using stem cells for regeneration.


Key Features

  • Highlights the molecular and evolutionary features of stem cells which make them so important to all biological research
  • Explores methods of isolation, characterization, activation, and maintenance of stem cells
  • Includes models for clinical application in regenerative medicine, cancer therapy, and transplantation


Stem cell biologists; developmental biologists; biomedical researchers including oncologists, cancer biologists, and researchers using stem cells for regeneration

Table of Contents

  • Quotes
  • Preface
  • Acknowledgments
  • Introduction: Special Remarks
    • 1. What Entity Could Be Called a Stem Cell?
      • 1.1. First Notions of Morphologically Nonrecognizable Cells Exhibiting a High Proliferative and Differentiation Potential
      • 1.2. Hematopoiesis as a Paradigmatic Case
      • 1.3. Functional Definition of Stem Cell Entity
      • 1.4. Quest for the Phenotype Definition of HSC: Quest for the Holy Grail
      • 1.5. LSK (KLS) Case
      • 1.6. Stem Cells from Other Tissues: Mesenchymal Stem Cell Example
    • 2. In Situ Normoxia versus “Hypoxia”
      • 2.1. Physioxia (Normoxia In Situ)
      • 2.2. Dissolved and Pericellular O2 Concentration in Culture
      • 2.3. Hypoxia
      • 2.4. Confusion Created by Considering the Atmospheric O2 Concentration as “Normoxia” in Ex Vivo Cell Studies
  • Part One. Anaerobiosis and Stem Cell Entity
    • 3. The “Hypoxic” Stem Cell Niche
      • 3.1. Embryonic and Fetal Development
      • 3.2. “Hypoxic” Stem Cell Niche during the Postnatal Life
      • 3.3. Location and “Hypoxic” Character of HSC and Their Niche
      • 3.4. Low Oxygen Stem Cell Niche in Other Tissues
    • 4. Low O2 Concentrations and the Maintenance of Stem Cells Ex Vivo
      • 4.1. First Notions of Oxygenation Ex Vivo
      • 4.2. Oxygenation Level and Ex Vivo Cultures of the Embryonic, Fetal, and Adult Cells
      • 4.3. Oxygenation Level and Culture of Stem and Progenitor Cells
      • 4.4. Conclusions
    • 5. Quiescence/Proliferation Issue and Stem Cell Niche
      • 5.1. Embryo and Embryonic Cells
      • 5.2. Stem Cells in “Hypoxic Niche”—Quiescence and/or Slow Proliferation; Case of Hematopoietic Stem Cells
      • 5.3. Mesenchymal Stem Cell Case
      • 5.4. Conclusions
    • 6. Metabolic Peculiarities of the Stem Cell Entity: Energetic Metabolism and Oxidative Status
      • 6.1. Embryonic Stem Cells
      • 6.2. Adult Stem Cells
      • 6.3. Oxidative Status of the Stem Cells
      • 6.4. Technical Limitations in the Stem Cell Metabolic Studies
    • 7. Molecular Basis of “Hypoxic” Signaling, Quiescence, Self-Renewal, and Differentiation in Stem Cells
      • 7.1. Stem Cell Signaling Transducing Pathways Triggered by Extrinsic Factors
      • 7.2. Intrinsic Factors Associated with Stem Cell Maintenance
      • 7.3. “Hypoxic Signaling” in Stem Cell Maintenance
      • 7.4. Epigenetic Regulation of the Stem Cell Fate
      • 7.5. Conclusion
  • Part Two. Anaerobic-to-Aerobic Eukaryote Evolution: A Paradigm for Stem Cell Self-Renewal, Commitment and Differentiation?
    • 8. Evolution of Eukaryotes with Respect to Atmosphere Oxygen Appearance and Rise: Anaerobiosis, Facultative Aerobiosis, and Aerobiosis1
      • 8.1. From the First Prokaryotes to the Great Oxidation Event
      • 8.2. Appearance of Eukaryotes, First Eukaryotic Common Ancestor, Last Eukaryotic Common Ancestor, and Diversification of Eukaryotes
      • 8.3. Neoproterozoic Oxygenation Event and Metazoan Controversy
      • 8.4. Cambrian Period, Further Increase in Atmospheric O2 Concentration, Paleozoic Era, and Definitive Stabilization 650Million Years Ago
      • 8.5. Conclusions
    • 9. Evolution of Mitochondria in Eukaryotes versus Mitochondria “Maturing” from the Stage of Stem Cells to Committed Progenitors and Mature Cells1
      • 9.1. Integration of Bacterial Endosymbiont and the Acquisition of Aerobic Respiration: A Simultaneous or Two-Step Process?
      • 9.2. Organelle of Mitochondrial Origin
      • 9.3. Anaerobic Respiration Is More Primitive Than Aerobic
      • 9.4. Mitochondria Issue and Stem Cells
      • 9.5. Conclusions
    • 10. Evolutionary Origins of Stemness: Relationship between Self-Renewal and Ancestral Eukaryote Biology; Conservation of Self-Renewal Principle in Parallel with Adaptation to O2
      • 10.1. Stemness as Perceived on the Basis of Mammalian Studies
      • 10.2. Stem Cells in Bilateria
      • 10.3. Stemness in Basal Metazoans
      • 10.4. Stemness Features in Protists
      • 10.5. The Oxygen and Stem Cell Entity
      • 10.6. The Oxygen Evolutionary Paradigm and Stemness
      • 10.7. Integrative Model of Stemness
    • 11. Metabolic and Genetic Features of Ancestral Eukaryotes versus Metabolism and “Master Pluripotency Genes” of Stem Cells
      • 11.1. Ancestral Energetic Character of the Stem Cells
      • 11.2. Genetic Features of Ancestral Eukaryotes with Respect to “Master Pluripotency Genes” of Stem Cells
      • 11.3. Evolution of HIF Pathway
      • 11.4. Conclusion
    • 12. Other Features Concerning the Analogy “Stem Cells: Primitive Eukaryotes”: ABC Transporters’ Anaerobiosis/Stemness Link
      • 12.1. ATP-Binding Cassette Transporters
      • 12.2. The Physiological Role of ABC Transporters
      • 12.3. ABC Transporters and Their Connection with Anaerobiosis and Stemness
      • 12.4. ABC Transporters, Protist Anaerobiosis/Microaerophilia, and Life Cycle
      • 12.5. Conclusion
    • 13. Harnessing Anaerobic Nature of Stem Cells for Use in Regenerative Medicine
      • 13.1. Ex Vivo Approximation of Physiological Oxygenation
      • 13.2. Cultures Exposed to Physiologically Relevant Oxygenation or to Hypoxia in Cell Therapy
      • 13.3. Conclusions
    • 14. Cancer Stem Cell Case and Evolutionary Paradigm
      • 14.1. Concept of Cancer Stem Cell
      • 14.2. Metabolic Aspect of Cancer and Cancer Stem Cells versus Normal Tissue Stem Cells
      • 14.3. Multidrug Resistance Phenomenon
      • 14.4. Tissue Migration (“Invasiveness”), Circulation, and “Seeding”: A General Stem Cell Property
      • 14.5. Evolutionary Roots of Cancer: Link with Stemness
      • 14.6. Primary Cause of Cancer
  • Index


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© Academic Press 2016
1st November 2015
Academic Press
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About the Authors

Zoran Ivanovic

Zoran Ivanovic

Zoran Ivanovic is Scientific Director of French Blood Institute for the regions of Aquitaine and Limousin (Bordeaux, France) and Head of R&D Cell Engineering Research Laboratory. He is also the Group Leader (“Adult stem cells”) in UMR 5164 CNRS/University of Bordeaux. He received his MD, MSc (system and comparative physiology) and DSc (experimental hematology) degrees at Belgrade University, and the highest French Degree “HDR” (Habilitation à Diriger les Recherches) at Bordeaux 2 University. He specialized in Transfusion (Bordeaux 2 University) and in Cell Therapy (Paris 7 University). Research Professor at Institute for Medical Research of Belgrade University, former Associate Professor of Hematology at Limoges and Bordeaux Universities (1999-2002), he has been, since 2011, guest professor at the Medical Faculty of Niš University. Dr Ivanovic obtained several grants in the field of cord blood and adult stem cell research. His group studies the anaerobic proliferation of stem cells and develops clinical-scale ex-vivo expansion procedures, pre-conditioning of stem cells for transplantation as well as new approaches of stem and progenitor cell conservation in hypothermia. He published 123 articles and book chapters, realized 150 meeting communications and supervised several PhD and master theses. He serves as Academic Editor of PLoS One as well as reviewer for many scientific journals.

Affiliations and Expertise

Scientific Director, French Blood Institute for the Regions of Aquitaine and Limousin (EFS-AL), Bordeaux, France; Head of Cell Engineering R&D Laboratory of EFS-AL; Group Leader (“Adult stem cells”) in UMR 5164 CNRS/University of Bordeaux, Bordeaux, France

Marija Vlaski-Lafarge

Marija Vlaski-Lafarge

Marija Vlaski Lafarge is staff scientist in R&D Cell Engineering Research Laboratory of French Blood Institute for the regions of Aquitaine and Limousin (Bordeaux, France) and in UMR 5164 CNRS/University of Bordeaux. She obtained her PhD degree at Faculty of Sciences (Cell physiology), University of Belgrade, Serbia. Her scientific activity is devoted to stem cell metabolism and physiology studies. Dr. Vlaski Lafarge presented her work in articles, book chapters and meeting communications. She participated in the grants preparation, reviewed several scientific manuscripts, and governed many student’s research projects.

Affiliations and Expertise

Staff Scientist, Cell Engineering R&D Laboratory, French Blood Institute for the Regions of Aquitaine and Limousin (EFS-Aqli), Bordeaux, France; University of Bordeaux, Bordeaux, France


"...provides the key for understanding and predicting stem cell behavior in vivo and ex vivo, which is of paramount importance for the cell engineering and anti-cancer strategies." --Serbian Archives of Medicine

"The “evolutionary stem cell paradigm”of Z. Ivanović and M. Vlaški provides the key for understanding and predicting stem cell behavior in vivo and ex vivo, which is of paramount importance for the cell engineering and anti-cancer strategies. The concept of anaerobiosis and stemness presented in this unique book implies the epigenetic missing link in stem cells behavior. The evolutionary paradigm described, although partly hypothetical, is important for understanding developmental biology." --Professor Pavle Milenković, MD, PhD, President of the Academy of Medical Sciences, Serbian Medical Society

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