Over the past 15 years, mesenchymal stem cells (MSCs) have been assessed for their capacity to suppress inflammation and promote tissue repair. Regardless of whether the cells are primed (exposed to instructive cues) before administration, their phenotype will respond to environmental signals present in the pathophysiological setting being treated. Since hypoxia and inflammation coexist in the settings of acute injury and chronic diseases, we sought to explore how the proteome and metabolome of MSCs changes when cells were exposed to 48 h of 1% oxygen, interferon gamma (IFN-γ), or both cues together. We specifically focused on changes in cell metabolism, immune modulation, extracellular matrix secretion and modification, and survival capacity. IFN-γ promoted expression of anti-pathogenic proteins and induced MSCs to limit inflammation and fibrosis while promoting their own survival. Hypoxia instead led to cell adaption to low oxygen, including upregulation of proteins involved in anaerobic metabolism, autophagy, angiogenesis, and cell migration. While dual priming resulted in additive effects, we also found many instances of synergy. These data lend insight to how MSCs may behave after administration to a patient and suggest how priming cells beforehand could improve their therapeutic capacity.

在过去的15年中，已经评估了间充质干细胞（MSC）抑制炎症和促进组织修复的能力。不管细胞在给药前是否已启动（暴露于指导性提示），它们的表型都会对所治疗的病理生理环境中存在的环境信号作出反应。由于缺氧和炎症共存于急性损伤和慢性疾病的环境中，因此我们试图探索当细胞暴露于48％1％氧气，γ干扰素（IFN-γ）或两种提示的情况下，MSCs的蛋白质组和代谢组如何变化一起。我们特别关注细胞代谢，免疫调节，细胞外基质分泌和修饰以及存活能力的变化。IFN-γ促进抗病原蛋白的表达，并诱导MSC限制炎症和纤维化，同时促进自身生存。缺氧反而导致细胞适应低氧，包括上调参与厌氧代谢，自噬，血管生成和细胞迁移的蛋白质。虽然双重启动会产生累加效应，但我们也发现了许多协同效应。这些数据使人们对MSCs给予患者后的行为有了深刻的了解，并暗示了预先启动细胞如何改善其治疗能力。