Provincial Clinical Medical College of Fujian Medical University, Fuzhou, China.
Department of Hematology, Fujian Provincial Hospital, Fuzhou, China.
Cell Biochem Funct. 2020 Aug;38(6):792-800. doi: 10.1002/cbf.3548. Epub 2020 May 20.
The current study investigated the role of mesenchymal stem cells (MSCs) in repairing senile bone marrow injury and the underlying mechanism. Adenoviral vectors expressing green fluorescent protein (GFP) were used to label MSCs. The level of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were detected by thiobarbituric acid (TBA) and xanthine oxidation (XTO) methods. The proportions of CD34, CD3 cells, cell proliferation and apoptosis were determined by flow cytometry, Cell counting kit (CCK)-8 and comet assay. Tissues were stained by haematoxylin-eosin (HE) staining and their changes were observed under a transmission electron microscopy. Expression levels of age-related and autophagy-related genes were detected by RT-qPCR and Western Blot. MSCs were successfully implanted into the bone marrow of aging rats. We found that the SOD activity was increased and MDA content was reduced in MSCs group. The proportions of CD34 cells were significantly more in the MSCs group than those in the Model group, and bone marrow cell colony formation and cell viability were both greatly increased in MSCs group. The proportions of CD3 cells and level of Vascular endothelial growth factor (VEGF) were increased significantly, while IL-6 level was reduced greatly in MSCs group. Moreover, the bone marrow tissues of the model group were severely damaged, but those of the MSCs group were significantly improved. In addition, MSCs were involved in regulation of aging-related genes and autophagy-related genes. In conclusion, our findings showed that MSCs can repair bone marrow damage in aging rats, and regulate aging- and autophagy-related genes and immune response. SIGNIFICANCE: This study investigated the role of MSCs in the repair of senile bone marrow injury and the underlying mechanism. The effects of MSCs on physiological and biochemical indicators, cell function, tissue structure differences and pathological changes in aging rats were studied. It was found that MSCs can repair bone marrow damage in aging rats. MSCs regulate aging and autophagy-related genes and its involvement in immune response. Our findings improve the understandings on the regulatory mechanism of MSCs and provide key evidence for the study of MSCs in bone marrow repair.
本研究探讨了间充质干细胞（MSCs）在修复衰老性骨髓损伤中的作用及其潜在机制。采用腺病毒载体表达绿色荧光蛋白（GFP）对 MSCs 进行标记。通过硫代巴比妥酸（TBA）和黄嘌呤氧化（XTO）法检测丙二醛（MDA）水平和超氧化物歧化酶（SOD）活性。采用流式细胞术、细胞计数试剂盒（CCK-8）和彗星试验测定 CD34、CD3 细胞比例、细胞增殖和凋亡。采用苏木精-伊红（HE）染色对组织进行染色，并在透射电子显微镜下观察其变化。通过 RT-qPCR 和 Western Blot 检测与年龄相关和自噬相关基因的表达水平。MSCs 成功植入衰老大鼠骨髓。我们发现 MSCs 组 SOD 活性增加，MDA 含量减少。MSCs 组 CD34 细胞比例明显高于模型组，MSCs 组骨髓细胞集落形成和细胞活力均显著增加。CD3 细胞比例和血管内皮生长因子（VEGF）水平显著升高，IL-6 水平明显降低。此外，模型组的骨髓组织严重受损，而 MSCs 组则明显改善。此外，MSCs 参与调节衰老相关基因和自噬相关基因。综上所述，我们的研究结果表明，MSCs 可修复衰老大鼠骨髓损伤，并调节衰老和自噬相关基因以及免疫反应。意义：本研究探讨了 MSCs 在修复衰老性骨髓损伤中的作用及其潜在机制。研究了 MSCs 对衰老大鼠生理生化指标、细胞功能、组织结构差异和病理变化的影响。结果发现，MSCs 可修复衰老大鼠的骨髓损伤。MSCs 调节衰老和自噬相关基因及其参与免疫反应。我们的研究结果提高了对 MSCs 调节机制的认识，为 MSCs 在骨髓修复中的研究提供了关键证据。
