干細胞也“生銹”

*，空氣中的氧氣能夠通過氧化作用導(dǎo)致一些金屬生銹。與此類似，來自瑞典隆德大學(xué)的一個研究小組zui近發(fā)現(xiàn)處于發(fā)育過程中的一些細胞也會受到氧化作用的不良影響，氧化作用會導(dǎo)致細胞功能受到損傷。

研究人員利用實驗室內(nèi)的干細胞培養(yǎng)系統(tǒng)從多能干細胞誘導(dǎo)獲得了新的血細胞。他們希望未來能夠利用這套系統(tǒng)獲得包括造血干細胞在內(nèi)的新生血細胞，滿足需要進行骨髓移植的病人的需求。但是世界上許多實驗室發(fā)現(xiàn)利用培養(yǎng)的多能干細胞獲得的血細胞其功能表現(xiàn)不如捐獻者來源的血細胞，這些細胞雖然看起來正常，但是卻不能正常生長和擴增。

實驗室內(nèi)獲得的血細胞為何不能像捐獻者來源的血細胞一樣發(fā)揮正常功能呢？在對這一問題進行研究的過程中，隆德大學(xué)的研究人員在實驗室內(nèi)新獲得的血細胞中發(fā)現(xiàn)了高水平的活性氧簇（ROS，一類引起氧化作用的分子）。ROS的含量足以對細胞造成損傷，導(dǎo)致細胞無法在培養(yǎng)條件下生長。研究人員隨后開發(fā)了一套能夠降低細胞氧化損傷的因子雞尾酒，使用了這種因子雞尾酒之后新獲得的具有生長能力的造血干細胞數(shù)目是使用之前的超過20倍。

“我們發(fā)現(xiàn)在多能干細胞來源的新生血細胞中，氧化作用會造成細胞損傷導(dǎo)致不良影響，與此同時我們可能也找到了在獲得用于移植治療的造血干細胞的過程中面臨的zui大障礙。”領(lǐng)導(dǎo)該研究的Niels-Bjarne Woods這樣說道。

干細胞也“生銹”

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.

干細胞也“生銹”