Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Department of Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Int J Radiat Oncol Biol Phys. 2018 Apr 1;100(5):1259-1269. doi: 10.1016/j.ijrobp.2018.01.015. Epub 2018 Jan 9.
Human mesenchymal stromal cells (MSCs) may aid the regeneration of ionizing radiation (IR)-induced tissue damage. They can be harvested from different tissues for clinical purposes; however, the role of the tissue source on the radiation response of human MSCs remains unknown.
Human MSCs were isolated from adipose tissue, bone marrow, and umbilical cord, and cellular survival, proliferation, and apoptosis were measured after irradiation. The influence of IR on the defining functions of MSCs was assessed, and cell morphology, surface marker expression, and the differentiation potential were examined. Western blot analyses were performed to assess the activation of DNA damage signaling and repair pathways.
MSCs from adipose tissue, bone marrow, and umbilical cord exhibited a relative radioresistance independent of their tissue of origin. Defining properties including cellular adhesion and surface marker expression were preserved, and irradiated MSCs maintained their potential for multilineage differentiation irrespective of their tissue source. Analysis of activated DNA damage recognition and repair pathways demonstrated an efficient repair of IR-induced DNA double-strand breaks in MSCs from different tissues, thereby influencing the induction of apoptosis.
These data show for the first time that MSCs are resistant to IR and largely preserve their defining functions after irradiation irrespective of their tissue of origin. Efficient repair of IR-induced DNA double-strand breaks and consecutive reduction of apoptosis induction may contribute to the tissue-independent radiation resistance of MSCs.
间充质基质细胞（MSCs）可能有助于电离辐射（IR）引起的组织损伤的再生。它们可以从不同的组织中采集用于临床目的；然而，组织来源对人 MSCs 的辐射反应的作用尚不清楚。
从脂肪组织、骨髓和脐带中分离出人 MSCs，并在照射后测量细胞存活、增殖和凋亡。评估 IR 对 MSCs 定义功能的影响，并检查细胞形态、表面标记表达和分化潜能。进行 Western blot 分析以评估 DNA 损伤信号转导和修复途径的激活。
脂肪组织、骨髓和脐带来源的 MSCs 表现出相对的放射抗性，而与组织来源无关。包括细胞黏附和表面标记表达在内的定义特性得以保留，并且无论其组织来源如何，辐照 MSCs 都保持其多能分化的潜能。对激活的 DNA 损伤识别和修复途径的分析表明，不同组织来源的 MSCs 能够有效地修复 IR 诱导的 DNA 双链断裂，从而影响细胞凋亡的诱导。
这些数据首次表明，MSCs 对 IR 具有抗性，并且在照射后很大程度上保留其定义功能，而与组织来源无关。IR 诱导的 DNA 双链断裂的有效修复以及随后的细胞凋亡诱导减少可能有助于 MSCs 的组织非依赖性辐射抗性。
