School of Engineering and Materials Science, Queen Mary University of London, London, UK.
J Cell Physiol. 2011 Oct;226(10):2562-70. doi: 10.1002/jcp.22605.
Human mesenchymal stem cells (MSCs) reside under hypoxic conditions in vivo, between 4% and 7% oxygen. Differentiation of MSCs under hypoxic conditions results in inhibited osteogenesis, while chondrogenesis is unaffected. The reasons for these results may be associated with the inherent metabolism of the cells. The present investigation measured the oxygen consumption, glucose consumption and lactate production of MSCs during proliferation and subsequent differentiation towards the osteogenic and chondrogenic lineages. MSCs expanded under normoxia had an oxygen consumption rate of ∼98 fmol/cell/h, 75% of which was azide-sensitive, suggesting that these cells derive a significant proportion of ATP from oxidative phosphorylation in addition to glycolysis. By contrast, MSCs differentiated towards the chondrogenic lineage using pellet culture had significantly reduced oxygen consumption after 24 h in culture, falling to ∼12 fmol/cell/h after 21 days, indicating a shift towards a predominantly glycolytic metabolism. By comparison, MSCs retained an oxygen consumption rate of ∼98 fmol/cell/h over 21 days of osteogenic culture conditions, indicating that these cells had a more oxidative energy metabolism than the chondrogenic cultures. In conclusion, osteogenic and chondrogenic MSC cultures appear to adopt the balance of oxidative phosphorylation and glycolysis reported for the respective mature cell phenotypes. The addition of TGF-β to chondrogenic pellet cultures significantly enhanced glycosaminoglycan accumulation, but caused no significant effect on cellular oxygen consumption. Thus, the differences between the energy metabolism of chondrogenic and osteogenic cultures may be associated with the culture conditions and not necessarily their respective differentiation.
人骨髓间充质干细胞（MSCs）在体内处于低氧环境中，氧分压为 4%至 7%。在低氧条件下分化的 MSCs 导致成骨作用受到抑制，而软骨形成不受影响。这些结果的原因可能与细胞的固有代谢有关。本研究测量了 MSCs 在增殖过程中和随后向成骨和软骨谱系分化过程中的耗氧量、葡萄糖消耗和乳酸生成。在常氧条件下扩增的 MSCs 的耗氧率约为 98 fmol/细胞/h，其中 75%对叠氮化物敏感，表明这些细胞除糖酵解外，还从氧化磷酸化中获得大量 ATP。相比之下，使用微球培养法向软骨谱系分化的 MSCs 在培养 24 小时后氧耗显著降低，培养 21 天后降至约 12 fmol/细胞/h，表明向主要依赖糖酵解的代谢转变。相比之下，在成骨培养条件下，MSCs 在 21 天的时间内保持约 98 fmol/细胞/h 的耗氧率，表明这些细胞比软骨谱系培养具有更高的氧化能量代谢。总之，成骨和软骨 MSC 培养物似乎采用了与各自成熟细胞表型报道的氧化磷酸化和糖酵解平衡。TGF-β 添加到软骨微球培养物中显著增加了糖胺聚糖的积累，但对细胞耗氧量没有显著影响。因此，软骨和成骨培养物之间能量代谢的差异可能与培养条件有关，而不一定与其各自的分化有关。
