Islam Mohammad S, Stemig Melissa E, Takahashi Yutaka, Hui Susanta K
School of Dentistry, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN 55455, USA.
Masonic Cancer Center, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN 55455, USA.
J Radiat Res. 2015 Mar;56(2):269-77. doi: 10.1093/jrr/rru098. Epub 2014 Nov 24.
Mesenchymal stem cells (MSCs) isolated from human pluripotent stem cells are comparable with bone marrow-derived MSCs in their function and immunophenotype. The purpose of this exploratory study was comparative evaluation of the radiation responses of mesenchymal stem cells derived from bone marrow- (BMMSCs) and from human embryonic stem cells (hESMSCs). BMMSCs and hESMSCs were irradiated at 0 Gy (control) to 16 Gy using a linear accelerator commonly used for cancer treatment. Cells were harvested immediately after irradiation, and at 1 and 5 days after irradiation. Cell cycle analysis, colony forming ability (CFU-F), differentiation ability, and expression of osteogenic-specific runt-related transcription factor 2 (RUNX2), adipogenic peroxisome proliferator-activated receptor gamma (PPARγ), oxidative stress-specific dismutase-1 (SOD1) and Glutathione peroxidase (GPX1) were analyzed. Irradiation arrested cell cycle progression in BMMSCs and hESMSCs. Colony formation ability of irradiated MSCs decreased in a dose-dependent manner. Irradiated hESMSCs showed higher adipogenic differentiation compared with BMMSCs, together with an increase in the adipogenic PPARγ expression. PPARγ expression was upregulated as early as 4 h after irradiation, along with the expression of SOD1. More than 70% downregulation was found in Wnt3A, Wnt4, Wnt 7A, Wnt10A and Wnt11 in BMMSCs, but not in hESMSCs. hESMSCs are highly proliferative but radiosensitive compared with BMMSCs. Increased PPARγ expression relative to RUNX2 and downregulation of Wnt ligands in irradiated MSCs suggest Wnt mediated the fate determination of irradiated MSCs.
从人多能干细胞中分离出的间充质干细胞（MSCs）在功能和免疫表型上与骨髓来源的MSCs相当。本探索性研究的目的是比较评估骨髓来源的间充质干细胞（BMMSCs）和人胚胎干细胞来源的间充质干细胞（hESMSCs）的辐射反应。使用常用于癌症治疗的直线加速器，将BMMSCs和hESMSCs在0 Gy（对照）至16 Gy的剂量下进行辐照。辐照后立即以及辐照后1天和5天收获细胞。分析细胞周期、集落形成能力（CFU-F）、分化能力以及成骨特异性的 runt相关转录因子2（RUNX2）、脂肪生成性过氧化物酶体增殖物激活受体γ（PPARγ）、氧化应激特异性超氧化物歧化酶-1（SOD1）和谷胱甘肽过氧化物酶（GPX1）的表达。辐照使BMMSCs和hESMSCs的细胞周期进程停滞。辐照后的MSCs集落形成能力呈剂量依赖性下降。与BMMSCs相比，辐照后的hESMSCs表现出更高的脂肪生成分化能力，同时脂肪生成性PPARγ表达增加。辐照后4小时，PPARγ表达上调，同时SOD1表达也上调。在BMMSCs中，Wnt3A、Wnt4、Wnt 7A、Wnt10A和Wnt11的表达下调超过70%，但在hESMSCs中未出现这种情况。与BMMSCs相比，hESMSCs具有高增殖性但对辐射敏感。辐照后的MSCs中PPARγ相对于RUNX2的表达增加以及Wnt配体的下调表明Wnt介导了辐照后MSCs的命运决定。
