Ahead of their time: hyperoxia injury induces senescence in developing lung fibroblasts

摘要

Besides broadening our appreciation for the contribution of senescence to the hyperoxia response in the developing lung, this article makes a significant methodologic contribution to those studying hyperoxia lung injury. Hyperoxia is used extensively to model bronchopulmonary dysplasia in vitro and in vivo (8). With in vitro systems there is often significant variability in what oxygen exposure defines "normoxia" in tissue culture conditions. While laboratories have historically cultured cells at 21% O2, there is a growing appreciation that cells in the body typically grow under less oxygen tension than that provided by media incubated at 21% O2, and that fetal cells are accustomed to growing with even lower oxygen exposure than cells derived from adult subjects (3). For this reason, stem cells are often cultured and differentiated in vitro at 1-5% O2, and prior reports in other tissues suggest that 5% O2 may represent tissue culture normoxia, with partial pressures of oxygen more consistent with what cells encounter in the organism (3). In this article, cells cultured at 40% demonstrated increased senescence features when compared with cells cultured at 21%. Additional experiments showed that cells cultured at 21% had a significantly increased senescent phenotype when compared with 5%, suggesting that the contribution of oxygen to the senescent phenotype was dose dependent, and that cell culture at 21% was sufficient to elicit some senescent features.