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Therapeutic Efficacy of Human Umbilical Cord Mesenchymal Stem Cells Combined with Pirfenidone in Pulmonary Fibrosis Mice
Wu Xian1, Peng Danyi1, Gou Hao1, Liu Jiang1, Zou Wenjing1, Zhou Ou1, Ding Fengxia2, Tian Daiyin2, Fu Zhou1,2*, Zou Lin3
1Department of Pediatric Research Institute, Childrenʼs Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China; 2Respiratory Center of Childrenʼs Hospital of Chongqing Medical University, Chongqing 400014, China; 3Center for Clinical Molecular Medicine, Childrenʼs Hospital of Chongqing Medical University, Chongqing 400014, China
Abstract: This study aims to investigate the therapeutic effect of human umbilical cord mesenchymal stem cells combined with pirfenidone in bleomycin-induced pulmonary fibrosis in mice and its possible mechanism. C57BL/6 mice were divided into normal control group， hUC-MSCs control group， model group， 30 mg/kg PFD group (P30)， 100 mg/kg PFD group， 300 mg/kg PFD group， hUC-MSCs treatment group and hUC-MSCs combined with P30 group. 5×105 hUC-MSCs were injected via the tail vein on the 7th day after intratracheal instillation of bleomycin and PFD was administered once a day orally from then on. Their lung tissues were harvested at the 21th day， pulmonary morphological changes and collagen deposition were assessed respectively by HE and Masson staining， the content of collagen was measured by Sircol assay and the levels of fibrosis related markers were detected by PCR and Western blot. In addition， myofibroblasts (MFB) were cultured with hUC-MSCs conditional medium (CM) collected by ultrafiltration and PFD in vitro， CCK-8 and Brdu assay were used to detect the growth and proliferation of MFB. The results showed that hUC-MSCs combined with P30 group significantly improved the survival rate and pulmonary histopathology of mice， reduced the levels of collagen and fibrosis related markers (P<0.001)， and the efficacy of combination therapy was better than that of PFD alone and hUC-MSCs alone (P<0.05). PFD partially inhibited proliferation of MFB and PFD combined with CM enhanced the inhibitory effect of PFD on proliferation (P<0.001). This study demonstrate that hUC-MSCs combined with low-dose PFD may attenuate bleomycin-induced pulmonary fibrosis in mice by inhibiting MYB proliferation.
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