13 - Harnessing Anaerobic Nature of Stem Cells for Use in Regenerative Medicine

Abstract

The traditional cultures at atmospheric O2 concentration (“normoxia”—in fact, “hyperoxia”) result in high differentiation rate and exhaustion of stem cells by their differentiation, which is another paradigmatic case reflecting evolution of primary eukaryotes toward the organisms better adapted to oxygen. The main advances in the clinical-scale ex vivo expansion procedures of hematopoietic stem and progenitor cells are related to “hypoxic response” (i.e., “primitive” or “ancestral” modality of cellular functioning) leading to the maintenance of stemness. These include signaling via Notch, HOXB4, Wnt and Hedgehog, pharmacologic stabilization of HIF-1α, antioxidative treatment, and activation of anaerobic glycolysis/attenuation of oxidative phosphorylation in mitochondria. Manipulations of these very primary cellular functions including the switch between anaerobic and aerobic metabolism, and related activation of an ancestral part of genome and transcriptome, are becoming the major tools in manipulation of stem cells for regenerative medicine. So-called “hypoxic” preconditioning of stem cells, progenitors, and postprogenitor cell populations for tissue regeneration showed great interest since it enables improvement of not only survival when transplanted in a physiological tissue environment, hypoxic, and ischemic zones, but also enhancement of their proliferative capacities and modulation of their differentiation potential as well as their secretory characteristics improving the in vivo beneficial effect.