4 years ago

Effect of Tumor Necrosis Factor Alpha Dose and Exposure Time on Tumor Necrosis Factor Induced Gene-6 Activation by Neonatal and Adult Mesenchymal Stromal Cells.

John E Davies, Yunqing Li, Shiva Hamidian Jahromi
Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) is a major anti-inflammatory mediator released by activated mesenchymal stromal cells (MSCs). Neonatal MSCs are considered more metabolically active than cells derived from adult tissues, and potentially less heterogeneous. We hypothesized that a TNF-α activated neonatal MSC population (human umbilical cord perivascular cells-HUCPVCs) would show an enhanced level of TSG-6 activation compared to adult bone marrow MSCs (BMMSCs). Thus, we stimulated HUCPVCs, and both human and mouse BMMSCs with 1, 10, 50, and 100ng/mL of recombinant TNF-α over various exposure times. Supernatant, and total RNA, of the cells were collected for measurement of both TSG-6 RNA expression, and secreted TSG-6 protein. To compare gene levels quantification was done by normalizing the expression levels of TSG-6 to the geometric mean of the three most stable reference genes, out of a cohort of 30 tested genes, using the Pfaffl method. We found that HUCPVCs exhibited both an enhanced and more rapid response to low dose (1ng/mL) TNF-α exposure resulting in ~11.5-fold increase in TSG-6 expression within the first 30 minutes. In contrast, hBMMSCs showed 2-fold increase by 1 hour that increased to 9.5-fold with a higher (50ng/mL) TNF-α exposure for the same time. mBMMSCs showed a 2-fold increase after 24 hours that was independent of TNF-α concentration. Thus, although TSG-6 expression level varied among donors, both hMSC populations exhibited enhanced TSG-6 upregulation, upon TNF-α stimulation, compared to mBMMSCs. In conclusion, HUCPVCs showed higher sensitivity, and a prompter response, to TNF-α stimulation compared with hBMMSCs. Thus, neonatal MSCs may be a stronger candidate population than those derived from adult bone marrow to treat inflammatory diseases.

Publisher URL: http://doi.org/10.1089/scd.2017.0179

DOI: 10.1089/scd.2017.0179

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