Mechanisms of regulation of transcription factor HIF under hypoxia.

The importance of transcription factor HIF in cellular response to hypoxia and various regulatory levels determining its functioning within cells are considered. Special attention is paid to important links of the hypoxia-triggered HIF-mediated mechanism. The review contains retrospective analysis of the search for cellular primary oxygen sensors and their interactions with HIF. It also deals with the interrelation of HIF-mediated and other hypoxia-activated mechanisms and outlines importance of HIF subunits in the cell.

Resistance of rat bone marrow mesenchymal stromal precursor cells to anoxia in vitro.

We studied the effect of significantly reduced oxygen content (0% O(2)in gaseous phase) in culture medium on rat bone marrow mesenchymal stromal precursor cells. The cells retained their morphology and expression of characteristic markers during several days under these conditions; they were viable, proliferated, and some cultured cells were even capable of realizing the initial stages of osteogenic and adipogenic differentiation. Further culturing of precursor cells under conditions of anoxia led to activation of apoptosis in cultures and to progressive necrosis.

[Mesenchymal stromal progenitor cells: general characteristics and functional state in low oxygen tension].

The promising use of multipotent mesenchymal stromal cells (MSC) in regenerative technologies accounts for necessity of detailed study and analysis of their physiology. Along with searching for MSC specific immunophenotype markers and factors that affect MSC heterogeneity, proliferative activity, self-renewal capacity and differentiation potential, progenitor, the cells functioning in low oxygen tension present one the open-ended problems. The specific response of progenitor cells to hypoxia seems to depend on many factors including their commitment and differentiation status, tissue type as well as the nature of the hypoxic impact. Interestingly, it was shown that low oxygen tension can be used as a factor regulating MSC proliferation, viability and differentiation.

[Heterogeneity of stromal precursor cells isolated from rat bone marrow].

Bone marrow stroma contains mesenchymal stem cells (MSC) which are precursor for at least mesenchyma-derived cells. Recent investigations revealed a lot of questions concerning MSC biology that should be further refined. The aim of this study was the comparative analysis of rat bone marrow stroma cells cultures. Mesenchymal precursor cells isolated from rat bone marrow were passed up to 50 times. Comparative morphological and immunophenotypical analysis of these cultures was carried out as well as their ability to osteogenic differentiation was studied. The isolated cultures contained morphologically different types of cells and thus showed a high heterogenity level. Morphology of these cell types was described. The heterogeneity level was reported to decrease over time. It was found out that subcultures isolated from different rats shared the same immunophenotype characteristics (CD90+, CD44+, CD54+, CD 106+, CD45-, CD11b-), but differed in their morphology as well as in ability to osteogenic differentiation. Thus MSC identification requires more specific marker and functional tests to be used.

Effect of hypoxia on stromal precursors from rat bone marrow at the early stage of culturing.

We studied the effect of hypoxia on stromal precursors from rat bone marrow. Under hypoxic conditions the cultures were characterized by low heterogeneity, the percent of large spread morphologically different cells decreased. Hypoxia increased proliferative activity of cells, had no adverse effect, and decreased the percent of cells expressing hemopoietic markers.