Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells.
Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells.
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DOI：
10.3390/ijms14012119
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发表时间：
2013-01-22
影响因子：
5.6
通讯作者：
Giorgio M
中科院分区：
文献类型：
--
作者：
Berniakovich I;Giorgio M
间充质干细胞（MSC）培养条件的优化对于MSC在再生医学中的应用具有重要意义。O2调节细胞生物学的各个方面，并且在体内，MSC暴露于不同的O2浓度，从骨髓龛中的非常低的张力到伤口中的较高量。在我们目前的工作中，我们分离出小鼠骨髓基质细胞（BMSC），并表明它们含有符合MSC定义要求的细胞群。为了建立低O2对细胞特性的影响，我们研究了缺氧（3%O2）条件下培养的BSMC。我们的研究结果表明，3% O2增强BMSC的增殖，以及在集落形成单位测定（CFU-A）中的集落形成，静止细胞的百分比，以及干细胞标记物雷克斯-1和Oct-4的表达，从而表明暴露于缺氧时培养物的干细胞性增加。与此相反，内在分化过程被抑制3%O2。分化的总产量取决于O2张力对BMSC培养的特定阶段的调节。因此，我们建立了一个有效的BMSC在体外分化的策略，使用细胞增殖的初始阶段在3%O2，然后分化阶段在21%O2。我们还证明，3%O2影响BMSC分化的p53和活性氧（ROS）的非依赖性途径。我们的研究结果可以显着有助于获得高质量的MSC有效的细胞治疗。
Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O2 on cellular properties, we examined BSMC cultured under hypoxic (3% O2) conditions. Our results demonstrate that 3% O2 augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3% O2. Overall yield of differentiation was dependent on the adjustment of O2 tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O2, followed by differentiation stage at 21% O2. We also demonstrated that 3% O2 affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.
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影响因子：
8
作者：
Pan, Y;Oprysko, PR;Simon, MC
通讯作者：
Simon, MC
影响因子：
4.8
作者：
Berniakovich, Ina;Trinei, Mirella;Giorgio, Marco
通讯作者：
Giorgio, Marco
影响因子：
6.5
作者：
Meirelles, LD;Nardi, NB
通讯作者：
Nardi, NB
DOI：
10.1073/pnas.81.17.5468
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BERNLOHR, DA;ANGUS, CW;KELLY, TJ
通讯作者：
KELLY, TJ
影响因子：
3.4
作者：
Chow, DC;Wenning, LA;Papoutsakis, ET
通讯作者：
Papoutsakis, ET