Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
Int J Radiat Oncol Biol Phys. 2013 Dec 1;87(5):1171-8. doi: 10.1016/j.ijrobp.2013.09.003. Epub 2013 Oct 23.
Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown.
Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays.
MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR.
These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression.
间充质干细胞(MSCs)具有迁移到病变部位并分化为功能性组织的能力。虽然这种功能对于放射治疗后的组织再生可能很重要,但电离辐射(IR)对细胞存活以及分化和间充质干细胞特征的功能方面的影响在很大程度上仍然未知。
检查了来自健康志愿者和原代人成纤维细胞的人原代 MSCs 的辐射敏感性,并评估了暴露于 IR 后细胞形态、细胞周期效应、细胞凋亡和分化潜能。使用基因芯片研究了暴露于 IR 后 MSC 的干细胞基因表达模式。
MSCs 不比人原代成纤维细胞更敏感,但个体 MSC 之间的辐射敏感性存在很大差异。IR 不会明显改变细胞形态、细胞骨架结构和细胞迁移能力。即使在高达 10 Gy 的高辐射剂量下,MSCs 仍保持其分化潜能。与原代成纤维细胞相比,MSCs 未显示照射诱导的细胞凋亡增加。基因表达分析显示,涉及 DNA 损伤反应和 DNA 修复的各种基因上调,但 IR 对已建立的 MSC 表面标志物的表达似乎只有轻微影响。
这些数据表明,人 MSCs 不比分化的原代成纤维细胞更敏感。此外,在光子照射下,MSCs 能够在功能水平上以及在干细胞标志物表达方面保留其定义的干细胞特征。