Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells.

Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells.
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DOI:
10.1186/1478-811x-8-18
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发表时间:
2010-07-16
期刊:
Cell communication and signaling : CCS
影响因子:
--
通讯作者:
Hass R
Hass R
中科院分区:
其他
文献类型:
--
作者:
Lavrentieva A;Majore I;Kasper C;Hass R

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在低氧条件下(1.5%至5%氧气(O2))培养不同来源的人脐带间充质干细胞(MSC)后,与常氧水平(21%O2)下的相同培养物相比,耗氧率降低2至3倍。同时测定了4种不同供体骨髓间充质干细胞培养上清液中的溶解氧,范围从1.5%O2时的15μμ/L到常氧21%O2时的196 Mol/L。与常氧培养相比,不同低氧培养的MSC群体的增殖能力增强。这一效应与低氧条件下细胞损伤或细胞死亡的显著减少是平行的,通过细胞释放LDH来评估,即caspase3/7活性的测量显示不同培养物之间的凋亡细胞死亡几乎没有差异。低氧条件下的骨髓间充质干细胞培养与低氧诱导因子-1α的诱导和能量代谢相关基因GLUT-1、LDH和PDK1的表达上调有关。与此同时,在低氧培养的MSC中可以观察到显著增加的葡萄糖消耗和相应的乳酸产生,这表明这些人类干细胞在低氧环境中的新陈代谢发生了变化。
Following cultivation of distinct mesenchymal stem cell (MSC) populations derived from human umbilical cord under hypoxic conditions (between 1.5% to 5% oxygen (O2)) revealed a 2- to 3-fold reduced oxygen consumption rate as compared to the same cultures at normoxic oxygen levels (21% O2). A simultaneous measurement of dissolved oxygen within the culture media from 4 different MSC donors ranged from 15 μmol/L at 1.5% O2 to 196 μmol/L at normoxic 21% O2. The proliferative capacity of the different hypoxic MSC populations was elevated as compared to the normoxic culture. This effect was paralleled by a significantly reduced cell damage or cell death under hypoxic conditions as evaluated by the cellular release of LDH whereby the measurement of caspase3/7 activity revealed little if any differences in apoptotic cell death between the various cultures. The MSC culture under hypoxic conditions was associated with the induction of hypoxia-inducing factor-alpha (HIF-1α) and an elevated expression of energy metabolism-associated genes including GLUT-1, LDH and PDK1. Concomitantly, a significantly enhanced glucose consumption and a corresponding lactate production could be observed in the hypoxic MSC cultures suggesting an altered metabolism of these human stem cells within the hypoxic environment.