Acute Hypoxic Stress Affects Migration Machinery of Tissue O₂-Adapted Adipose Stromal Cells

Abstract

The ability of mesenchymal stromal (stem) cells (MSCs) to be mobilised from their local depot towards sites of injury and to participate in tissue repair makes these cells promising candidates for cell therapy. Physiological O2 tension in an MSC niche in vivo is about 4–7%. However, most in vitro studies of MSC functional activity are performed at 20% O2. Therefore, this study focused on the effects of short-term hypoxic stress (0.1% O2, 24 h) on adipose tissue-derived MSC motility at tissue-related O2 level. No significant changes in integrin expression were detected after short-term hypoxic stress. However, O2 deprivation provoked vimentin disassembly and actin polymerisation and increased cell stiffness. In addition, hypoxic stress induced the downregulation of ACTR3, DSTN, MACF1, MID1, MYPT1, NCK1, ROCK1, TIAM1, and WASF1 expression, the products of which are known to be involved in leading edge formation and cell translocation. These changes were accompanied by the attenuation of targeted and nontargeted migration of MSCs after short-term hypoxic exposure, as demonstrated in scratch and transwell migration assays. These results indicate that acute hypoxic stress can modulate MSC function in their native milieu, preventing their mobilisation from sites of injury.

Gene expression is implicated in the ability of pikas to occupy Himalayan elevational gradient

“…While there were no enriched GO categories or KEGG pathways in the down-regulated gene set, we also further investigated these genes through a literature search. We found that a number of these genes are known to be down-regulated in response to hypoxia in human cells, such as PLA2G4C [66] and MACF1 [67]. We also found that some of these genes are potentially related to immune response such as HNRNPR which positively regulates MHC class 1 expression [68], DOCK8 which is important in the functioning of natural killer cells and receptor-γt-positive innate lymphoid cells [69,70], and ELF1 which plays a role in the functioning and development of lymphocytes [71].…”

Expansion of adipose tissue‐derived stromal cells at “physiologic” hypoxia attenuates replicative senescence

“…Proliferative activity was assessed as population doubling time (PDT), measured in hours, and was calculated according to the following equation: PDT = (T-T0)*log 2/(log N-log N0), where (T-T0) is the duration of experiment (in hours), N is a number of cells at the end of the experiment, and N0 is a number of cells seeded initially. [22][23][24] Cells were seeded at standard density (3 × 10 3 cells/cm 2 ). Cell number was determined using a hemocytometer at day 0 and day 7.…”

IFN‐gamma priming of adipose‐derived stromal cells at “physiological” hypoxia

“…We successfully demonstrated that tissue O 2 ‐adapted ASCs are resistant to short‐term hypoxia, which can ensure their effective involvement in the regeneration of tissue damage under significant oxygen deprivation (Andreeva, Lobanova, Udartseva, & Buravkova, ). Further study revealed an attenuation of targeted and non‐targeted migration of ASCs after O 2 deprivation (Udartseva et al, ). These data appeared to be quite surprising as earlier acute hypoxic exposure of ambient (20%) O 2 ‐adapted MSCs was shown to enhance migration rate (Buravkova, Andreeva, Gogvadze, & Zhivotovsky, ).…”