Protective effects of BMSCs in combination with erythropoietin in bronchopulmonary dysplasia-induced lung injury.
Bronchopulmonary dysplasia (BPD) is the most common type of chronic lung disease in infancy, for which no effective therapy is currently available. The aim of the present study was to investigate the effect of treatment with bone marrow mesenchymal stem cells (BMSCs) in combination with recombinant human erythropoietin (rHuEPO) on BPD‑induced mouse lung injury, and discuss the underlying mechanism. The BPD model was established by the exposure of neonatal mice to continuous high oxygen exposure for 14 days, following which 1x106 BMSCs and 5,000 U/kg rHuEPO were injected into the mice 1 h prior to and 7 days following exposure to hyperoxia. The animals received four treatments in total (n=10 in each group). After 14 days, the body weights, airway structure, and levels of matrix metalloproteinase‑9 (MMP‑9) and vascular endothelial growth factor (VEGF) were detected using histological and immunohistochemical analyses. The effect on cell differentiation was observed by examining the presence of platelet endothelial cell adhesion molecule (PECAM) and VEGF using immunofluorescence. Compared with the administration of BMSCs alone, the body weight, airway structure, and the levels of MMP‑9 and VEGF were significantly improved in the BMSCs/rHuEPO group. The results of the present study demonstrated that the intravenous injection of BMSCs significantly improved lung damage in the hyperoxia‑exposed neonatal mouse model. Furthermore, the injection of BMSCs in combination with intraperitoneal injection of rHuEPO had a more marked effect, compared with BMSCs alone, and the mechanism may be mediated by the promoting effects of BMSCs and EPO. The results of the present study provided information, which may assist in future clinical trials.
Department of Pediatrics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Zhao-Hua
ZH
Zhang
Department of Pediatrics, Qilu Children's Hospital of Shandong University, Jinan, Shandong 066600, P.R. China.
Yan-Yan
YY
Pan
Department of Internal Medicine, Xinji Central Hospital, Changli, Hebei 250000, P.R. China.
Rui-Sheng
RS
Jing
Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Yun
Y
Luan
Department of Pediatrics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Luan
L
Zhang
Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Chao
C
Sun
Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Feng
F
Kong
Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Kai-Lin
KL
Li
Department of Pediatrics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Yi-Biao
YB
Wang
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001997:Bronchopulmonary Dysplasia / Q000150:complications*; D018929:Cell Culture Techniques; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D016130:Immunophenotyping; D055370:Lung Injury / Q000209:etiology* / Q000473:pathology* / Q000628:therapy; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015703:Antigens, CD; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D020780:Matrix Metalloproteinase 9