Anaerobiosis and Stemness

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. 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.

TABLE OF CONTENTS:PREFACESPECIAL REMARKS1) What entity could be called a “stem cell”?2) In situ “normoxia” vs. “hypoxia”Part I:ANAEROBIOSIS AND STEM CELL ENTITY1) The “hypoxic” stem cell niche2) Low O2 concentrations and the maintenances of stem cells ex vivo 3) Quiescence/proliferation issue and stem cell niche4) Metabolic peculiarities of the stem cell entity: energetic metabolism and oxidative status5) “Hypoxic” signaling, metabolic type, quiescence, self-renewal and differentiation

Part II:ANAEROBIC-TO-AEROBIC EUKARYOTE EVOLUTION – A PARADIGM FOR STEM CELL SELF-RENEWAL, COMMITMENT AND DIFFERENTIATION?1) Evolution of eukaryotes with respect to the appearance and rise of oxygen in the atmosphere: anaerobiosis, facultative aerobiosis and aerobiosis 2) Evolution of mitochondria in eukaryotes and mitochondria “maturing” from stem cells to committed progenitors and mature cells3) Evolutionary origins of stemness: relationship between self-renewal and ancestral eukaryote biology; conservation of self-renewal principle in parallel with the adaptation to O24) Metabolic and genetic features of ancestral eukaryotes vs. metabolism and “master pluripotency genes” of stem cells5) Some other features concerning the analogy "stem cells - primitive eukaryotes": ABC transporters’ anaerobiosis/stemness link6) Harnessing anaerobic nature of stem cells for the use in regenerative medicine 7) Cancer stem cell case and evolutionary paradigm