期刊
ARCHIVES OF BIOLOGICAL SCIENCES
卷 71, 期 2, 页码 201-208出版社
INST BIOLOSKA ISTRAZIVANJA SINISA STANKOVIC
DOI: 10.2298/ABS181117001L
关键词
mesenchymal stromal cells; oxygen deprivation; miRNA-210; HIF-1 alpha; HIF-2 alpha
类别
资金
- Ministry of Education, Science and Technological Development of the Republic of Serbia [III41004]
- EFS French Blood Institute
- French Ministry of Foreign Affairs [UMR 3427/US 005]
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-1 alpha and HIF-2 alpha 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-1 alpha and HIF-2 alpha 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.
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