KMID : 1204720220150040395
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International Journal of Stem Cells 2022 Volume.15 No. 4 p.395 ~ p.404
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Human Umbilical Cord-Derived Mesenchymal Stem Cells Repair SU5416-Injured Emphysema by Inhibiting Apoptosis via Rescuing VEGF-VEGFR2-AKT Pathway in Rats
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Chen Qin
Lv Lu Zheng Chujie Pan Huiwen Xu Jili Lin Jiang Deng Zhaoqun Qian Wei
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Abstract
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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.
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KEYWORD
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Apoptosis, COPD, Emphysema, SU5416, VEGF-VEGFR2-AKT pathway, hUC-MSCs.
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