Qin Chen1, Lu Lv2, Chujie Zheng3, Huiwen Pan2, Jili Xu3, Jiang Lin1, Zhaoqun Deng1, Wei Qian3. 1. Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China. 2. Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China. 3. Department of Otolaryngology-Head and Neck Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.
Abstract
BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a common, frequently-occurring disease and poses a major health concern. Unfortunately, there is current no effective treatment for COPD, particularly emphysema. Recently, experimental treatment of COPD using mesenchymal stem cells (MSCs) mainly focused on bone marrow-derived MSCs (BM-MSCs). Human umbilical cord-derived MSCs (hUC-MSCs) have more advantages compared to BM-MSCs. However, studies on the role of hUC-MSCs in management of COPD are limited. This study sought to explore the role of hUC-MSCs and its action mechanisms in a rat model of VEGF receptor blocker SU5416-injured emphysema. METHODS AND RESULTS: hUC-MSCs were characterized by immunophenotype and differentiation analysis. Rats were divided into four groups: Control, Control＋MSC, SU5416 and SU5416＋MSC. Rats in model group were administered with SU5416 for three weeks. At the end of the second week after SU5416 administration, model group were infused with 3×106 hUC-MSCs through tail vein. After 14 days from hUC-MSCs transplantation, rats were euthanized and data were analyzed. HE staining and mean linear intercepts showed that SU5416-treated rats exhibited typical emphysema while emphysematous changes in model rats after hUC-MSCs transplantation disappeared completely and were restored to normal phenotype. Furthermore, hUC-MSCs inhibited apoptosis as shown by TUNEL and Western blotting. ELISA and Western blotting showed hUC-MSCs rescued VEGF-VEGFR2-AKT pathway in emphysematous lungs. CONCLUSIONS: The findings show that hUC-MSCs effectively repair the emphysema injury. This study provides the first evidence that hUC-MSCs inhibit apoptosis via rescuing VEGF- VEGFR2-AKT pathway in a rat model of emphysema.
BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a common, frequently-occurring disease and poses a major health concern. Unfortunately, there is current no effective treatment for COPD, particularly emphysema. Recently, experimental treatment of COPD using mesenchymal stem cells (MSCs) mainly focused on bone marrow-derived MSCs (BM-MSCs). Human umbilical cord-derived MSCs (hUC-MSCs) have more advantages compared to BM-MSCs. However, studies on the role of hUC-MSCs in management of COPD are limited. This study sought to explore the role of hUC-MSCs and its action mechanisms in a rat model of VEGF receptor blocker SU5416-injured emphysema. METHODS AND RESULTS: hUC-MSCs were characterized by immunophenotype and differentiation analysis. Rats were divided into four groups: Control, Control＋MSC, SU5416 and SU5416＋MSC. Rats in model group were administered with SU5416 for three weeks. At the end of the second week after SU5416 administration, model group were infused with 3×106 hUC-MSCs through tail vein. After 14 days from hUC-MSCs transplantation, rats were euthanized and data were analyzed. HE staining and mean linear intercepts showed that SU5416-treated rats exhibited typical emphysema while emphysematous changes in model rats after hUC-MSCs transplantation disappeared completely and were restored to normal phenotype. Furthermore, hUC-MSCs inhibited apoptosis as shown by TUNEL and Western blotting. ELISA and Western blotting showed hUC-MSCs rescued VEGF-VEGFR2-AKT pathway in emphysematous lungs. CONCLUSIONS: The findings show that hUC-MSCs effectively repair the emphysema injury. This study provides the first evidence that hUC-MSCs inhibit apoptosis via rescuing VEGF- VEGFR2-AKT pathway in a rat model of emphysema.