Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation

Darija Lončarić, Biljana Stanković, Amani Ghousein, Miša Vreća, Vesna Spasovski, Arnaud Villacreces, Christelle Debeissat, Christophe Grosset, Zoran Ivanović, Sonja Pavlović


Paper description:

  • Cultivation of human bone marrow derived mesenchymal stromal cells (hBM MStroC) expanded at oxygen deprivation conditions increases their efficiency in tissue regeneration.
  • We report a significant increase in miRNA-210 expression during prolonged hBM MStroC expansion at oxygen deprivation, and the involvement of hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2) in miRNA-210 expression regulation.
  • This is the first study on the expression of miRNA-210 in extended exposure of hBM MStroC to oxygen deprivation, indicating miRNA-210 as a good candidate for a hypoxia-mimicking approach in stem cell therapy.

Abstract: A major limitation in the development of efficient clinical protocols for mesenchymal stromal cell (MStroC)-based tissue regeneration therapy is the low retention and survival of MStroC in injured tissue after therapeutic administration. Low oxygen concentration preconditioning(LOP) during ex vivo cultivation of MStroC, as a method for mimicking oxygenation in their physiological microenvironment, has been shown to be beneficial in clinical trials using MStroC. Introducing hypoxia-mimicking molecules into MStroC during cultivation could be an advantageous LOP strategy. MicroRNA (miRNA) drugs are good candidates for this approach. Analysis of the expression of miRNA-210 in human bone marrow-derived MStroC in conditions of acute and extended hypoxia (24 to 72 h) was performed using RT-qPCR methodology. HIF-1α and HIF-2α gene knockdown cell lines were generated using lentiviral transduction of short hairpin RNA (shRNA) in order to examine whether miRNA-210 expression is regulated by transcription factor HIF-1 and/or HIF-2. We detected a significant increase in miRNA-210 expression in hypoxic conditions at time points of 24, 48 and 72 h (p˂0.05). Knocking down of HIF-1α and HIF-2α genes indicated involvement of both transcription factors in the elevation of miRNA-210 expression. These results point to miRNA-210 as a good candidate for a hypoxia-mimicking molecule in LOP strategy.

Received: November 17, 2018; Revised: January 6, 2019; Accepted: January 8, 2019; Published online: January 14, 2019

How to cite this article: Lončarić D, Stanković B, Ghousein A, Vreća M, Spasovski V, Villacreces A, Debeissat C, Grosset CF, Ivanović Z, Pavlović S. Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation. Arch Biol Sci. 2019;71(2):201-8.


mesenchymal stromal cells; oxygen deprivation; miRNA-210; HIF-1α; HIF-2α

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