Mesenchymal stem cells in combination with erythropoietin repair hyperoxia-induced alveoli dysplasia injury in neonatal mice via inhibition of TGF-β1 signaling

// Yun Luan 1 , Luan Zhang 2 , Sun Chao 1 , Xiaoli Liu 3 , Kaili Li 1 , Yibiao Wang 2 , Zhaohua Zhang 2 1 Central Research Laboratory, The Second Hospital of Shandong University, Jinan, China 2 Department of Pediatrics, The Second Hospital of Shandong University, Jinan, China 3 Department of Hematology, The Second Hospital of Shandong University, Jinan, China Correspondence to: Yibiao Wang, e-mail: wangyibiao@sdu.edu.cn Zhaohua Zhang, e-mail: zhaohuaz1972@126.com Keywords: BPD, MSCs, EPO, TGF-β1, ETM Received: December 09, 2015 Accepted: April 11, 2016 Published: May 12, 2016 ABSTRACT The aim of the present study is to investigate the protection effects of bone marrow mesenchymal stem cells (MSCs) in combination with EPO against hyperoxia-induced bronchopulmonary dysplasia (BPD) injury in neonatal mice. BPD model was prepared by continuous high oxygen exposure, 1×10 6 bone marrow MSCs and 5000U/kg recombinant human erythropoietin (EPO) were injected respectively. Results showed that administration of MSCs, EPO especially MSCs+EPO significant attenuated hyperoxia-induced lung damage with a decrease of fibrosis, radical alveolar counts and inhibition of the occurrence of epithelial-mesenchymal transition (EMT). Furthermore, MSCs+EPO co-treatment more significantly suppressed the levels of transforming growth factor-β1(TGF-β1) than MSCs or EPO alone. Collectively, these results suggested that MSCs, EPO in particular MSCs+EPO co-treatment could promote lung repair in hyperoxia-induced alveoli dysplasia injury via inhibition of TGF-β1 signaling pathway to further suppress EMT process and may be a promising therapeutic strategy.