Yang Lei, Liu Ziling, Chen Chen, Cong Xiaofeng, Li Zhi, Zhao Shasha, Ren Meng
Cancer Center, The First Hospital of Jilin UniversityChangchun 130021, China.
Am J Transl Res. 2017 Apr 15;9(4):1914-1921. eCollection 2017.
Low-dose radiation (LDR) has been known to stimulate cell proliferation. The effect of LDR on human bone marrow mesenchymal stem cells (BMSCs), however, remains to be determined. The current study, therefore, aimed to investigate the effect of LDR on human BMSC proliferation and its mechanisms. To accomplish this, human BMSCs were isolated from ribs and cultured with or without exposition to LDR (75 mGy) for 24 h. Cell proliferation was assessed by MTT assay, the cytokines secreted by the BMSCs were quantified by ELISA, and the proteins associated with cell proliferation and cell cycle were evaluated by immunoblot analysis. BMSCs isolated from human ribs were capable of differentiating into osteoblasts and adipocytes. LDR stimulated human BMSC proliferation (0.580 ± 0.106 vs 0.419 ± 0.026 on day 4, < 0.05; 0.794 ± 0.025 vs 0.689 ± 0.047 on day 7, < 0.05) and increased S-phase proportion. LDR significantly enhanced the production of SCF, GM-CSF, and IL-11. Moreover, BMSCs modulated T-cell proliferation, and LDR further augmented the modulatory effect of BMSCs on T-cell proliferation. Cell cycle-associated proteins, such as Rb, CDK1, and CDC25B, appeared to mediate the stimulatory effect of LDR on BMSC proliferation. The findings of the current study indicate that physical stimulants, such as LDR, could be used for the large-scale expansion of human BMSCs, and thus may be used for MSC cellular therapy in clinic.
低剂量辐射(LDR)已知可刺激细胞增殖。然而,LDR对人骨髓间充质干细胞(BMSCs)的影响仍有待确定。因此,本研究旨在探讨LDR对人BMSC增殖的影响及其机制。为此,从肋骨中分离出人BMSCs,并在有或无LDR(75 mGy)照射24小时的情况下进行培养。通过MTT法评估细胞增殖,通过ELISA法定量BMSCs分泌的细胞因子,并通过免疫印迹分析评估与细胞增殖和细胞周期相关的蛋白质。从人肋骨分离的BMSCs能够分化为成骨细胞和脂肪细胞。LDR刺激人BMSC增殖(第4天0.580±0.106对0.419±0.026,<0.05;第7天0.794±0.025对0.689±0.047,<0.05)并增加S期比例。LDR显著增强了SCF、GM-CSF和IL-11的产生。此外,BMSCs调节T细胞增殖,LDR进一步增强了BMSCs对T细胞增殖的调节作用。细胞周期相关蛋白,如Rb、CDK1和CDC25B,似乎介导了LDR对BMSC增殖的刺激作用。本研究结果表明,物理刺激物,如LDR,可用于人BMSCs的大规模扩增,因此可能用于临床的MSC细胞治疗。