Abstract:
Objective To explore the therapeutic effect and mechanism of umbilical cord mesenchymal stem cells (UC-MSC) in rats with primary graft dysfunction after lung transplantation.
Methods Twenty-four male Lewis rats were randomly divided into donor and recipient groups, with 12 rats in each group. The recipients were further divided into 3 groups: blank control group, negative control group, and treatment group, with 4 rats in each group. The color, size and texture of the transplanted lungs were observed 72 h after lung transplantation. The ventilation status and progression of consolidation in the transplant lungs of rats in each group were evaluated by micro-CT. Plasma, transplant lung tissue and alveolar lavage fluid samples of recipient rats were collected. The wet/dry ratio of lung tissue was measured to evaluate the degree of pulmonary edema. Hematoxylin-eosin (HE) staining was used to evaluate the degree of lung tissue damage. Terminal deoxyribonucleic acid transferase mediated dUTP nick end labeling (TUNEL) staining was used to evaluate cell apoptosis. Myeloperoxidase (MPO) activity in lung tissue was detected, and enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α levels in plasma and alveolar lavage fluid.
Results The appearance of the transplant lungs in the negative control group was significantly different from that of the autologous lungs, while the transplant lungs in the treatment group were almost identical in color to the autologous lungs compared to the blank control group. Compared with the negative control group, the treatment group showed reduced alveolar exudate and more intact airway epithelial cell structure. No alveolar exudate was observed in the blank control group, and the structure of the airways and alveoli remained normal. The treatment group had lower apoptosis rate of airway epithelial cells, lung tissue wet/dry ratio, and MPO activity compared to the negative control group (all P < 0.05). The levels of IL-6 and TNF-α in the bronchoalveolar lavage fluid of the treatment group were lower than those in the negative control group, while the level of IL-10 was higher than that in the negative control group and the blank control group (all P < 0.05). There were no statistically significant differences in the levels of cytokines in plasma among each group (all P > 0.05).
Conclusions UC-MSC may effectively alleviate the severity of primary graft dysfunction in rats by reducing the apoptosis rate of cells in lung tissue and inhibiting inflammatory responses.