Concise Review: The Role of Oxygen in Hematopoietic Stem Cell Physiology

Abstract

Molecular dioxygen, O(2), is an important element in cellular microenvironment in vivo, and often overlooked in standard in vitro and ex vivo cell culture systems. Molecular oxygen is the ultimate electron acceptor in oxidative cellular respiration, and also a signal that regulates cell fate through concentration gradients. Recent advances in physiology of oxygen and adult stem cell research have shown that apart from being important for oxidative phosphorylation, thus energy metabolism, oxygen is also important as a signaling molecule and an integral part of the stem cell niche. This review article covers the influence of physiologically relevant oxygen levels on adult stem cells through highlighting the research on the effect of oxygen concentration on hematopoietic stem cell maintenance, proliferation and differentiation. This is important particularly to understand the embryonic and adult stem cell biology and physiology. The new discoveries in this field will help to further improve current tissue engineering and clinical applications. In addition, understanding the relationship between oxygen and stemness is invaluable for the advanced treatments of neoplastic diseases. Authors believe that in the future, active and programmed dynamic of oxygen levels will be routinely used for the programmed in vitro and ex vivo expansion of different adult stem cell types and tissue regeneration purposes.

3D models of the hematopoietic stem cell niche under steady-state and active conditions

“…Therefore, it appears that a combination of a lower oxygen but higher cytokine availability influenced HSPC behavior in the static culture towards an enhanced maintenance of CD34 + cells. This conclusion fits to previous reports showing that hypoxia supports HSC maintenance and quiescence 35, 79–81 and that the availability of soluble factors that enables autocrine and/or paracrine signaling is an important determinant in HSC cultures 82 , particularly in biomaterial-approaches in which the cells are maintained in confined spaces 83 . Perfusion, in contrast, seemed to foster hematopoietic differentiation within the 3D scaffolds, as seen by the expression of CD71, a marker specific for erythroid progenitors.…”

“…In this way soluble factors have a tremendous effect on HSC behavior and fate 31, 32 . Furthermore, the reduced availability of oxygen due to hypoxia in the bone marrow as well as the availability of specific nutrients are critical for the niche to function 33–35 . The flow of blood and liquid inside of the niche applies a certain shear stress and mechanical forces 36 .…”

In Vitro Detection of Hypoxia Using a Ratiometric Quantum Dot-Based Oxygen Sensor

“…1 While reactive oxygen species are toxic to all organisms, 2 O 2 is none-the-less necessary for ATP generation in aerobic cells 3 and for several other physiological functions. Low O 2 concentrations result in hypoxia, which is observed in tumor tissues 4 due to the fact that cancer cells rapidly consume oxygen as they produce energy via a high rate glycolysis (i.e.…”

Metabolic Modification in Gastrointestinal Cancer Stem Cells: Characteristics and Therapeutic Approaches

“…Oxygen concentration is tightly regulated at both tissue and cellular levels because of its essential role in many biological processes (Parks et al, ; Sermeus et al, ; Jež et al, ). The low oxygen tension can have extensive downstream transcriptional effects, such as activation of pro‐apoptotic and pro‐angiogenic pathways, and generally provides strong selective pressure for tumor growth and promotes survival of the most aggressive malignant cells (Parks et al, ; Sermeus et al, ).…”