Análise transcritômica de perfil metabólico de células-tronco mesenquimais adiposas em hipóxia e normóxia

Abstract

Adipose tissue-derived mesenchymal stem cells (hAMSC) are promisor therapeutic tool for regenerative medicine and chronic inflammatory diseases treatment due to its multipotency and immunomodulatory properties. However, to achieve the maximum potential of hAMSC in clinical trials, is necessary to understand the interplay of these cells with the environmental elements, such as the oxygen. Oxygen is a factor that participates in the regulation of metabolism and cell biology; however, how oxygen can affect hAMSC is not completely understood. In this work, a transcriptional analysis and a systems biology approaches was applied to evaluate the effects of atmospheric oxygen in hAMSC during 14 days of exposure, by comparing the initial time (21% [O2] 0 d) and the final time (21% [O2] 14d). Likewise, hAMSC were evaluated considering others oxygen concentrations, such as 5% (5% [O2]) and 1% (1% [O2]), which were compared to 21% [O2] at final time (14d). Our data suggest that minor alterations in biological processes occur comparing between 21% [O2] 14d and 21% [O2] 0d, in term of differential expression. Genes related to cytokines and prostaglandins synthesis were upregulated suggesting an increased immunomodulatory effect over time. When was compared 21% [O2] vs 1% [O2] 14d, the normoxic condition showed downregulation of genes related to glycolysis and proliferation, as well as increased expression of genes associated with leucine catabolism, cholesterol synthesis, glutaminolysis, serine synthesis, oxidative stress, intrinsic apoptosis response and proliferation. The comparison with 5% [O2] demonstrated that normoxic hASMC is under oxidative stress condition and activation of DNA 5 damage response. In conclusion, oxygen may have major effects in hAMSC at low concentration by shifting metabolism and the synthesis of molecules that coordinate alterations in regulation of hAMSC biology.