干细胞也“生锈”
时间：2016-11-04 阅读：859
*，空气中的氧气能够通过氧化作用导致一些金属生锈。与此类似，来自瑞典隆德大学的一个研究小组zui近发现处于发育过程中的一些细胞也会受到氧化作用的不良影响，氧化作用会导致细胞功能受到损伤。
研究人员利用实验室内的干细胞培养系统从多能干细胞诱导获得了新的血细胞。他们希望未来能够利用这套系统获得包括造血干细胞在内的新生血细胞，满足需要进行骨髓移植的病人的需求。但是世界上许多实验室发现利用培养的多能干细胞获得的血细胞其功能表现不如捐献者来源的血细胞，这些细胞虽然看起来正常，但是却不能正常生长和扩增。
实验室内获得的血细胞为何不能像捐献者来源的血细胞一样发挥正常功能呢？在对这一问题进行研究的过程中，隆德大学的研究人员在实验室内新获得的血细胞中发现了高水平的活性氧簇（ROS，一类引起氧化作用的分子）。ROS的含量足以对细胞造成损伤，导致细胞无法在培养条件下生长。研究人员随后开发了一套能够降低细胞氧化损伤的因子鸡尾酒，使用了这种因子鸡尾酒之后新获得的具有生长能力的造血干细胞数目是使用之前的超过20倍。
“我们发现在多能干细胞来源的新生血细胞中，氧化作用会造成细胞损伤导致不良影响，与此同时我们可能也找到了在获得用于移植治疗的造血干细胞的过程中面临的zui大障碍。”领导该研究的Niels-Bjarne Woods这样说道。
Reactive Oxygen Species Impair the Function of CD90+ Hematopoietic Progenitors Generated from Human Pluripotent Stem Cells
Cell stressors, such as elevated levels of reactive oxygen species (ROS), adversely affect hematopoietic stem cell (HSC) reconstituting ability. However, the effects of ROS have not been evaluated in the context of hematopoietic development from human pluripotent stem cells (hPSCs). Using our previously described in vitro system for efficient derivation of hematopoietic cells from hPSCs, we show that the vast majority of generated hematopoietic cells display supraphysiological levels of ROS compared to fresh cord blood cells. Elevated ROS resulted in DNA damage of the CD34+ hematopoietic fraction and, following functional assays, reduced colony formation and impaired proliferative capacity. Interestingly, all the proliferative potential of the most primitive hematopoietic cells was limited to a small fraction with low ROS levels. We show that elevation of ROS in hPSC-derived hematopoietic cells is contributed by multiple distinct cellular processes. Furthermore, by targeting these molecular processes with 4 unique factors, we could reduce ROS levels significantly, yielding a 22-fold increase in the most primitive CD90+ CD34+ hematopoietic cells with robust growth capacity. We demonstrate that the ROS reducing factors specifically reduced ROS in more primitive hematopoietic fractions, in contrast to endothelial cells that maintained low ROS levels in the cultures. We conclude that high levels of ROS in in vitro differentiation systems of hPSCs is a major determinant in the lack of ability to generate hematopoietic cells with similar proliferation/differentiation potential to in vivo hematopoietic progenitors, and suggest that elevated ROS is a significant barrier to generating hPSC-derived repopulating HSCs. Stem Cells 2016.