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Chronic asthmatic condition modulated the onset of aging in bone marrow mesenchymal stem cells.

Morteza HeidarzadehRana KeyhanmaneshAysa RezabakhshReza RahbarghaziJafar RezaieShirin SaberianpourMehdi HasanpourAysan EslamiJafar SoleimanpourMahdi Ahmadi
Published in: Cell biochemistry and function (2021)
The emergence of an inflammatory condition such as asthma could affect the therapeutic potential of stem cells. Synopsis of previous documents yielded controversial outcomes, leading to a limitation of stem cell-based therapy in the clinical setting. This study aimed to assess the impact of asthmatic serum on the MSCs aging and dynamic growth in vitro. Rats were divided into control and asthmatic groups randomly. The asthmatic change was induced using OVA sensitization. The asthmatic structural changes are monitored by conventional Haematoxylin-Eosin staining. Thereafter, blood samples were taken and sera provided from each group. In this study, primary bone marrow mesenchymal stem cells were cultured in culture medium supplemented with normal and asthmatic serum for 7 days. The MSCs viability was examined using the MTT assay. The expression of the aging-related gene (β-galactosidase), and stemness-related markers such as Sox2, Kfl-4 and p16INK4a were analysed by real-time PCR assay. Histological examination revealed chronic inflammatory remodelling which is identical to asthmatic changes. MTT assay showed a reduction of mesenchymal stem cell viability compared to the control group (P < .05). Real-time PCR analysis revealed a down-regulation of stemness-related markers Sox2, Kfl-4 and p16INK4a coincided with aging changes (β-galactosidase) compared to the control group (P < .05). These data show the detrimental effect of asthmatic condition on bone marrow regenerative potential by accelerating early-stage aging in different stem cells and further progenitor cell depletion. SIGNIFICANCE OF THE STUDY: In such inflammatory conditions as asthma, the therapeutic potential of stem cells may be altered. We demonstrate that serum from asthmatic rats had the potential to reduce the viability of mesenchymal stem cells in vitro. Furthermore, we observed that the expression of the aging-related gene known β-galactosidase was statistically increased in cells co-cultured with asthmatic serum. At the same time, expression of stemness-related markers Sox2, Kfl-4 and p16INK4a down-regulated. These results support the damaging effect of asthmatic condition on bone marrow regenerative ability by inducing early-stage aging in stem cells and additional progenitor cell reduction.
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