Lakatos Kinga, Kalomoiris Stefanos, Merkely Béla, Nolta Jan A, Fierro Fernando A
Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
Institute for Regenerative Cures, University of California Davis, Sacramento, California.
J Cell Biochem. 2016 Feb;117(2):300-7. doi: 10.1002/jcb.25292.
Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells.
间充质干细胞（MSC）目前正在针对多种病症进行临床测试，大多数方法依赖于MSC分泌旁分泌信号来调节免疫系统、促进伤口愈合和诱导血管生成。缺氧已被证明会影响MSC的增殖、分化、存活和分泌谱。在此，我们研究了缺氧处理后人骨髓来源的MSC脂质组成的变化。我们使用质谱法比较了来自五个不同供体的MSC的脂质谱，这些MSC在常氧（对照）或缺氧（1%氧气）条件下培养两天。缺氧导致总甘油三酯、脂肪酸和二酰基甘油（DG）显著增加。值得注意的是，使用磷脂酰胆碱特异性磷脂酶C抑制剂D609降低DG水平可抑制血管内皮生长因子（VEGF）和血管生成素-2的分泌，但会增加白细胞介素-8的分泌，且对它们各自的mRNA水平无显著影响。在功能上，在缺氧条件下用D609孵育MSC会抑制细胞在伤口/划痕试验中促进人内皮细胞迁移的能力。因此，我们表明缺氧会导致MSC中DG增加，这可能会影响这些细胞的血管生成潜力。
