In vitro expansion affects the response of human bone marrow stromal cells to irradiation

作者：Yang Xiang, Chun Wu, Jiang Wu, Weili Quan, Chao Cheng, Jian Zhou, Li Chen, Lixin Xiang, Fengjie Li, Kebin Zhang, Qian Ran, Yi Zhang, Zhongjun Li · 发表于：Stem Cell Research & Therapy · 年份：2019 · DOI：10.1186/s13287-019-1191-3 · 被引用次数：14 · 研究领域：Mesenchymal stem cell research、Hematopoietic Stem Cell Transplantation、Tissue Engineering and Regenerative Medicine

BACKGROUND: Bone marrow stromal cells (BMSCs) are extensively used in regeneration therapy and cytology experiments simulate how BMSCs respond to radiation. Due to the small number and the heterogeneity of primary isolated BMSCs, extensive in vitro expansion is usually required before application, which affects the cellular characteristics and gene expression of BMSCs. However, whether the radiation response of BMSCs changes during in vitro expansion is unclear. METHODS: In this study, BMSCs were passaged in vitro and irradiated at passage 6 (P6) and passage 10 (P10). Then, apoptosis, the cell cycle, senescence, the cytokine secretion and the gene expression profile were analysed for the P6, P10, and non-irradiated (control) BMSCs at different post-irradiation time points. RESULTS: The P6 BMSCs had a lower percentage of apoptotic cells than the P10 BMSCs at 24 and 48 h post-irradiation but not compared to that of the controls at 2 and 8 h post-irradiation. The P6 BMSCs had a lower percentage of cells in S phase and a higher percentage in G1 phase than the P10 BMSCs at 2 and 8 h post-irradiation. The radiation had similar effects on the senescent cell level and impaired immunomodulation capacity of the P6 and P10 BMSCs. Regardless of whether they were irradiated, the P6 and P10 BMSCs always expressed a distinctive set of genes. The upregulated genes were enriched in pathways including the cell cycle, DNA replication and oocyte meiosis. Then, a subset of conserved irradiation r...