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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
International Journal of Stem Cells
Published online February 28, 2022;  
© 2022 Korean Society for Stem Cell Research.

Qin Chen1, Lu Lv2, Chujie Zheng3, Huiwen Pan2, Jili Xu3, Jiang Lin1, Zhaoqun Deng1, Wei Qian3

1Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
2Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
3Department of Otolaryngology-Head and Neck Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
Correspondence to: Wei Qian
Department of Otolaryngology-Head and Neck Surgery, Affiliated People’s Hospital of Jiangsu University, Dianli RD. 8, Zhenjiang 212002, China
Tel: +86-511-88917833, Fax: +86-511-85234387
E-mail: dwqian@yahoo.com
Received September 2, 2021; Revised January 19, 2022; Accepted January 24, 2022.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 : COPD, Emphysema, SU5416, hUC-MSCs, VEGF-VEGFR2-AKT pathway, Apoptosis


August 2022, 15 (3)