[Human placental mesenchymal stem cells of fetal origin relieves mouse pulmonary fibrosis via downregulating MyD88 and TGF-β signaling pathway].
Objective To investigate the therapeutic effect and mechanism of human placental mesenchymal stem cells of fetal origin (hfPMSCs) cultured in serum-free medium on mouse pulmonary fibrosis induced by bleomycin treatment. Methods Human hfPMSCs were cultured and identified by flow cytometry. Fifteen 6-week-old male SPF C57BL/6J mice were divided into 3 groups: bleomycin treatment group, hfPMSCs transplantation group and negative control group. Pulmonary fibrosis model was induced in the mice of bleomycin treatment group and hfPMSCs transplantation group with bleomycin (1 μg/L, 50 μL) via intratracheal instillation. The mice in negative control group were instilled with PBS (50 μL) through the same manner of the other two groups. Three days post-modelling, 200 μL containing 5×105hfPMSCs were injected into hfPMSCs transplantation group via tail vein. All the mice were sacrificed at day 21 after modeling in batch. Lung tissues were collected for analyzing the pathological changes by HE staining and Masson staining as well as detecting collagen content. The total protein of lung tissues was extracted for observing the expressions of myeloid differentiation factor 88 (MyD88) and transforming growth factor-β (TGF-β); the level of TGF-β in sera was determined by Western blotting. Results The hfPMSCs possessed the morphology of mesenchymal stem cells and expressed the surface markers CD73, CD90 and CD105, but did not express CD14, CD34 and CD45. HE and Masson staining showed that hfPMSCs transplantation significantly reduced the degree of pulmonary fibrosis compared with bleomycin treatment group. The collagen content and the expression levels of MyD88 and TGF-β in bleomycin treatment group were obviously higher than those in hfPMSCs transplantation group and negative control group. Conclusion hfPMSCs possess the capability of alleviating pulmonary fibrosis by down-regulating the expressions of MyD88 and TGF-β.
General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Jin
J
Tao
General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Qinglun
Q
Li
General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Xiaowei
X
Ma
General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Fei
F
Han
General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Xiaoming
X
Liu
General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Jun
J
Wei
General Hospital of Ningxia Medical University, Yinchuan 750004, China. *Corresponding author, E-mail: btxnxu05@163.com.
Yongzhao
Y
Zhu
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D005260:Female; D005333:Fetus / Q000166:cytology; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D053594:Myeloid Differentiation Factor 88; D053773:Transforming Growth Factor beta1