title: Strategies to Enhance Implantation and Survival of Stem Cells After Their Injection in Ischemic Neural Tissue.
abstract: High post-transplantation cell mortality is the main limitation of various approaches that are aimed at improving regeneration of injured neural tissue by an injection of neural stem cells (NSCs) and mesenchymal stromal cells (MStroCs) in and/or around the lesion. Therefore, it is of paramount importance to identify efficient ways to increase cell transplant viability. We have previously proposed the "evolutionary stem cell paradigm," which explains the association between stem cell anaerobic/microaerophilic metabolic set-up and stem cell self-renewal and inhibition of differentiation. Applying these principles, we have identified the main critical point in the collection and preparation of these cells for experimental therapy: exposure of the cells to atmospheric O2, that is, to oxygen concentrations that are several times higher than the physiologically relevant ones. In this way, the primitive anaerobic cells become either inactivated or adapted, through commitment and differentiation, to highly aerobic conditions (20%-21% O2in atmospheric air). This inadvertently compromises the cells' survival once they are transplanted into normal tissue, especially in the hypoxic/anoxic/ischemic environment, which is typical of central nervous system (CNS) lesions. In addition to the findings suggesting that stem cells can shift to glycolysis and can proliferate in anoxia, recent studies also propose that stem cells may be able to proliferate in completely anaerobic or ischemic conditions by relying on anaerobic mitochondrial respiration. In this systematic review, we propose strategies to enhance the survival of NSCs and MStroCs that are implanted in hypoxic/ischemic neural tissue by harnessing their anaerobic nature and maintaining as well as enhancing their anaerobic properties via appropriate ex vivo conditioning.
authors.affiliation: 1 Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway .
authors.forename: Ioanna
authors.initials: I
authors.lastname: Sandvig
authors.affiliation: 2 Innovation Center, Faculty of Mechanical Engineering, University of Belgrade , Belgrade, Serbia .|3 Belgrade Metropolitan University , Belgrade, Serbia .
authors.forename: Ivana
authors.initials: I
authors.lastname: Gadjanski
authors.affiliation: 4 French Blood Institute (EFS) , Aquitaine-Limousin Branch, Bordeaux, France .|5 U1035 INSERM/Bordeaux University , Bordeaux Cedex, France .
authors.forename: Marija
authors.initials: M
authors.lastname: Vlaski-Lafarge
authors.affiliation: 6 Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre Polish Academy Sciences, Warsaw, Poland .
authors.forename: Leonora
authors.initials: L
authors.lastname: Buzanska
authors.affiliation: 4 French Blood Institute (EFS) , Aquitaine-Limousin Branch, Bordeaux, France .|5 U1035 INSERM/Bordeaux University , Bordeaux Cedex, France .
authors.forename: Darija
authors.initials: D
authors.lastname: Loncaric
authors.affiliation: 6 Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre Polish Academy Sciences, Warsaw, Poland .
authors.forename: Ana
authors.initials: A
authors.lastname: Sarnowska
authors.affiliation: 4 French Blood Institute (EFS) , Aquitaine-Limousin Branch, Bordeaux, France .|5 U1035 INSERM/Bordeaux University , Bordeaux Cedex, France .
authors.forename: Laura
authors.initials: L
authors.lastname: Rodriguez
authors.affiliation: 1 Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway .|7 Division of Pharmacology and Clinical Neurosciences, Department of Neurosurgery and Clinical Neurophysiology, Umeå University Hospital , Umeå, Sweden .
authors.forename: Axel
authors.initials: A
authors.lastname: Sandvig
authors.affiliation: 4 French Blood Institute (EFS) , Aquitaine-Limousin Branch, Bordeaux, France .|5 U1035 INSERM/Bordeaux University , Bordeaux Cedex, France .
authors.forename: Zoran
authors.initials: Z
authors.lastname: Ivanovic
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000628:therapy*; D015687:Cell Hypoxia; D049109:Cell Proliferation; D006019:Glycolysis; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods*
keywords: anaerobiosis; hypoxia; ischemia; neural regeneration; stem cells; stroke