Mesenchymal stem cells repair bone marrow damage of aging rats and regulate autophagy and aging genes

Abstract

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.