PDF(Pubmed)
Abstract：
UNASSIGNED: Eltrombopag (EP) is a small molecule that acts directly on hematopoietic stem cells (HSCs) and megakaryocytes to stimulate the hematopoietic process. Mesenchymal stem/stromal cells (MSCs) are key hematopoietic niche regulators.
UNASSIGNED: We aimed to determine whether EP has any effect on MSC function and properties (especially on their hematopoietic-supporting ability) and if so, what changes (e.g. genome-wide transcriptomic alterations) are induced in MSC after EP treatment.
UNASSIGNED: MSCs were isolated from 12 healthy donors and treated with 15 µM and 50 µM of EP for 24 h. The toxicity of the drug on MSCs and their differentiation ability were analyzed, as well as the transcriptomic profile, reactive oxygen species (ROS) and DNA damage and the changes induced in the clonogenic capacity of HSCs.
UNASSIGNED: The results show that EP also modifies MSC functions, decreasing their adipogenic differentiation, increasing the expression of genes involved in hypoxia and other pathways related to oxygen homeostasis, and enhancing their ability to support hematopoiesis in vitro.
UNASSIGNED: Our findings support the use of EP in cases where hematopoiesis is defective, despite its well-known direct effects on hematopoietic cells. Our findings suggest that further studies on the effects of EP on MSCs from patients with aplastic anemia are warranted.
UNASSIGNED: We aimed to determine whether EP has any effect on MSC function and properties (especially on their hematopoietic-supporting ability) and if so, what changes (e.g. genome-wide transcriptomic alterations) are induced in MSC after EP treatment.
UNASSIGNED: MSCs were isolated from 12 healthy donors and treated with 15 µM and 50 µM of EP for 24 h. The toxicity of the drug on MSCs and their differentiation ability were analyzed, as well as the transcriptomic profile, reactive oxygen species (ROS) and DNA damage and the changes induced in the clonogenic capacity of HSCs.
UNASSIGNED: The results show that EP also modifies MSC functions, decreasing their adipogenic differentiation, increasing the expression of genes involved in hypoxia and other pathways related to oxygen homeostasis, and enhancing their ability to support hematopoiesis in vitro.
UNASSIGNED: Our findings support the use of EP in cases where hematopoiesis is defective, despite its well-known direct effects on hematopoietic cells. Our findings suggest that further studies on the effects of EP on MSCs from patients with aplastic anemia are warranted.
摘要：
UNASSIGNED：Eltrombopag（EP）是一种小分子，直接作用于造血干细胞（HSC）和巨核细胞以刺激造血过程。间充质干细胞/基质细胞(MSC)是关键的造血生态位调节因子。
UNASSIGNED：我们旨在确定EP是否对MSC的功能和性质（尤其是对其造血支持能力）有任何影响，如果有，EP治疗后MSC中诱导了哪些变化（例如全基因组转录组改变）。
UNASSIGNED：从12名健康供体中分离出MSCs，并用15µM和50µMEP处理24h。分析了药物对MSCs的毒性及其分化能力，以及转录组概况，活性氧（ROS）和DNA损伤以及诱导HSC克隆能力的变化。
UNASSIGNED：结果表明，EP还修改了MSC功能，减少他们的成脂分化，增加参与缺氧和其他与氧稳态相关途径的基因的表达，增强其体外支持造血的能力。
未经评估：我们的研究结果支持在造血功能有缺陷的情况下使用EP，尽管它对造血细胞有众所周知的直接作用。我们的发现表明，有必要进一步研究EP对再生障碍性贫血患者MSCs的影响。
UNASSIGNED：我们旨在确定EP是否对MSC的功能和性质（尤其是对其造血支持能力）有任何影响，如果有，EP治疗后MSC中诱导了哪些变化（例如全基因组转录组改变）。
UNASSIGNED：从12名健康供体中分离出MSCs，并用15µM和50µMEP处理24h。分析了药物对MSCs的毒性及其分化能力，以及转录组概况，活性氧（ROS）和DNA损伤以及诱导HSC克隆能力的变化。
UNASSIGNED：结果表明，EP还修改了MSC功能，减少他们的成脂分化，增加参与缺氧和其他与氧稳态相关途径的基因的表达，增强其体外支持造血的能力。
未经评估：我们的研究结果支持在造血功能有缺陷的情况下使用EP，尽管它对造血细胞有众所周知的直接作用。我们的发现表明，有必要进一步研究EP对再生障碍性贫血患者MSCs的影响。
