Effects of repeated transplantation of human umbilical cord mesenchymal stem cells in different time windows on silica-induced pulmonary fibrosis in rats

Objective To investigate the effect of repeated transplantation of human umbilical cord mesenchymal stem cells (HUCMSCs) at different time windows on pulmonary fibrosis in rats exposed to silica dust.

Methods Totally 48 healthy male SD rats were randomly divided into 4 groups (n=12), namely, control group, silicosis model group, early treatment group and late treatment group. Non-exposed endotracheal intubation was used to expose rats to 0.5 mL saline (control group) or 0.5 mL silica dust suspension(50 mg/mL mass concentration, the other groups)and repeated one time after a week. Furthermore, 0.5 mL HUCMSCs suspension (cell density 3.0×10⁹/L)were given by tail vein infusion at day 1, day 7, day 14, day 21 in the early treatment group, and at day 28, day 35, day 42, day 49 in the late treatment group after the first dust exposure. Rats in each group were euthanized on the 70 th day of the experiments. The pathological changes of lung tissues were observed by HE staining and Mason staining; the pulmonary fibrosis scores (Ashcroft scores) were marked; the lung coefficients were measured; the levels of lung tissue hydroxyproline(Hyp), transforming growth factor-beta 1(TGF-beta 1) and serum interleukin-6(IL-6) were measured.

Results Lung histopathology showed that the alveolar structure was normal in the control group, and fibrosis was observed in the other exposed groups, and cellular fibrous granuloma was observed in silicosis model group. Compared with silicosis model group, collagen fibers in both early and late treatment groups were significantly reduced. Compared with control group, the Aschcroft scores, lung coefficients, lung tissue Hyp, TGF-beta 1 and serum IL-6 in dust-exposed groups were significantly higher (P < 0.01), while those in the both early and late treatment groups were significantly lower than silicosis model group(P < 0.01). There were no significant differences of those indexes between early treatment group and late treatment group (P > 0.05).

Conclusion Repeated injection of HUCMSCs, whether in the stage of alveolitis or fibrosis predominated stage, could effectively alleviate silica-induced pulmonary fibrosis in rats.