International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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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

  • Qin Chen (Laboratory Center, Affiliated People's Hospital of Jiangsu University) ;
  • Lu Lv (Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University) ;
  • Chujie Zheng (Department of Otolaryngology-Head and Neck Surgery, Affiliated People's Hospital of Jiangsu University) ;
  • Huiwen Pan (Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University) ;
  • Jili Xu (Department of Otolaryngology-Head and Neck Surgery, Affiliated People's Hospital of Jiangsu University) ;
  • Jiang Lin (Laboratory Center, Affiliated People's Hospital of Jiangsu University) ;
  • Zhaoqun Deng (Laboratory Center, Affiliated People's Hospital of Jiangsu University) ;
  • Wei Qian (Department of Otolaryngology-Head and Neck Surgery, Affiliated People's Hospital of Jiangsu University)
  • Received : 2021.09.02
  • Accepted : 2022.01.24
  • Published : 2022.11.30
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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.

Keywords

Acknowledgement

This study was supported by the Youth Medical Talents Project of "Ke Jiao Qiang Wei" project of Jiangsu province (Grant number: QNRC2016449) and the "Innovative and Entrepreneurial Elite Team" Program (2016), Jiangsu, China.

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