Tissue-relevant O2 levels are considered as an important tool for the preconditioning of multipotent mesenchymal stromal cells (MSCs) for regenerative medicine needs. The present study investigated the quality and functions of the extracellular matrix (ECM) of MSCs under low O2 levels. Human adipose tissue-derived MSCs were continuously expanded under normoxia (20% O2, N) or "physiological" hypoxia (5% O2, Hyp). Decellularized ECM (dcECM) was prepared. The structure of the dcECM was analyzed using confocal laser and scanning electron microscopy. Collagen, dcECM-N, and dcECM-Hyp were recellularized with MSC-N and further cultured at normoxia. The efficacy of adhesion, spreading, growth, osteogenic potential, and paracrine activity of recellularized MSC-N were evaluated. At low O2, the dcECM showed an increased alignment of fibrillar structures and provided accelerated spreading of MSC-N, indicating increased dcECM-Hyp stiffness. We described O2-dependent "ECM-education" of MSC-N when cultured on dcECM-Hyp. This was manifested as attenuated spontaneous osteo-commitment, increased susceptibility to osteo-induction, and a shift in the paracrine profile. It has been suggested that the ECM after physiological hypoxia is able to ensure the maintenance of a low-commitment state of MSCs. DcECM, which preserves the competence of the natural microenvironment of cells and is capable of "educating" others, appears to be a prospective tool for guiding cell modifications for cell therapy and tissue engineering.

Decellularization

Regenerative Medicine

Hypoxia

10.3390/biomimetics8060476

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Citations (2)

[Immunomorphological study of the localization of types I, III, IV and V collagen in a primary culture of human aortic cells].

PubMed (1983)

Е. Р. Андреева Alexander N. Orekhov Domogatskiĭ Sp Idel'son Gl

Fibrosis is the most important manifestation of human vascular atherosclerosis. Primary culture of human aortic cells makes it possible to study some manifestations of fibrosis in vitro. Indirect immunofluorescence has shown that primary culture cells contain intracellular antigens to all the antibodies used but that only type I collagen forms extracellular matrix in culture. Modulation of the cultivation conditions does not lead to the appearance on the cell surface of other type collagens. It is assumed that in primary culture, human aortic cells synthesize the same collagen types as those synthesized in vitro. This circumstance might enable using such a culture as model for studying the mechanisms of fibrosis during atherosclerosis.

Primary culture

Immunofluorescence

Cell type

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Mesenchymal stem cells and hypoxia: Where are we?

Mitochondrion (2014)

Л. Б. Буравкова Е. Р. Андреева Vladimir Gogvadze Boris Zhivotovsky

Hypoxia

Regenerative Medicine

Ex vivo

10.1016/j.mito.2014.07.005

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Citations (125)

[PROFILE OF THE MARROW-DERIVED STROMAL PRECURSORS POPULATION IN C57BL/6N MICE FLOWN ON BIOSATELLITE BION-M1].

PubMed (2015)

E. A. Markina Bobyleva Pi Andrianova Е. Р. Андреева Л. Б. Буравкова

The CFU-F number, proliferative activity and spontaneous differentiation potential of stromal cells derived from the tibia marrow of C57BL/6N mice readapted to the 1-g gravity following a long-term flight on biosatellite Bion-M1 were evaluated. The CFU-F number, proliferative activity and spontaneous adipogenic and osteogenic differentiation of marrow-derived stromal cells from the space flown group were no different from the group of vivarium control. However, the proliferative activity and adhesion properties of the cells were down-regulated on day 7 of readaptation. These results suggest that space flight factors did not impact the stromal differon of the mouse marrow. The decline of stromal cells activity indicates the decompensation of their functions under 1g gravity.

Decompensation

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Citations (3)

Papaverine abolishes the atherogenic effect of the beta-blocker propranolol

Bulletin of Experimental Biology and Medicine (1992)

И. В. Андрианова M. D. Rekhter V.V. Tertov Е. Р. Андреева Alexander A. Mirоnоv

Beta blocker

BETA (programming language)

10.1007/bf00783112

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Evaluation of Cell Proliferation in Human Atherosclerotic Lesions

Humana Press eBooks (2003)

Е. Р. Андреева Alexander N. Orekhov

Local accumulation of cells (hypercellularity) in the intima of the arterial wall is recognized as one of the major manifestations of human atherosclerosis, which may result from local cell proliferation (1-3). This assumption was raised both on the comparative analysis of cell number in nondiseased and atherosclerotic areas of human arteries (3-5) and on the basis of the analysis of cell replication in experimental atherosclerosis (for review see ref. 1). In experimental atherosclerosis, cell replication was identified in several models, including mechanical injury of the arteries and experimental hypercholesterolemia. The experimental approach permits the direct determination of DNA replication using radiolabeled precursor-[(3)H]-thymidine, but it is impossible to demonstrate proliferation in human vessels directly, using standard procedures with labeling of replicating DNA. Villaschi and coworkers (6) labeled human arteries with [(3)H]-thymidine-ex vivo. They found a low level of replication in both grossly normal tissues and atherosclerotic plaques. In the case of ex vivo labeling, the questions of diffusion and of thymidine incorporation into ex vivo incubated tissue (6) make it difficult to be sure that this procedure reflects replication rates in vivo. Use of proliferation-specific antibodies is advantageous, since proliferating cells are detected directly. Antibodies to the cell-cycle related protein, PCNA (cyclin), are now commonly used in the study of human tissues (7-12). PCNA is an auxiliary protein of mammalian DNA polymerase-δ and is a stable cell-cycle-regulated nuclear protein (synthesized mainly in the S-phase but also present in G1 and G2 phases of the cell cycle), the presence of which correlates directly with a proliferative state of normal cells (7-9).

Ex vivo

Thymidine

10.1385/1-59259-073-x:213

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Citations (2)

Functional Activity of Non-Proliferating Mesenchymal Stromal Cells Cultured at Different Densities

Bulletin of Experimental Biology and Medicine (2021)

М. И. Ездакова Ksenia V. Zornikova С. В. Буравков Е. Р. Андреева

Mitomycin C

10.1007/s10517-021-05102-w

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Citations (3)