Wnt3a增强慢性阻塞性肺疾病大鼠模型中间充质干细胞的植入和分化

Wnt3a Enhances Mesenchymal Stem Cell Engraftment and Differentiation in a Chronic Obstructive Pulmonary Disease Rat Model.

作者信息

Wu Huala, Zhong Yulan, Li Yangjingsi, Zhou Xiangxiang, Zhao Tiantian, Wan Daomou, Zhu Yuanzhe, Zhang Zhiyan, Li Xiaolei, Gan Xin

机构信息

Department of Respiratory and Critical Care Medicine, Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.

Department of Respiratory and Critical Care Medicine, Chest Hospital of Jiangxi Province, Nanchang, Jiangxi, 330006, People's Republic of China.

出版信息

Int J Chron Obstruct Pulmon Dis. 2025 Jan 8;20:69-81. doi: 10.2147/COPD.S486262. eCollection 2025.

DOI:10.2147/COPD.S486262

PMID:39802038

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11725259/

Abstract

BACKGROUND

Bone marrow mesenchymal stem cell (BMSC) therapy is a novel approach for treating COPD. However, the difficulty in engraftment and easy clearance of BMSCs in vivo has hindered their clinical application. Hence, exploring effective methods to improve the engraftment and differentiation rates of BMSCs in vivo is urgent.

METHODS

We constructed BMSCs overexpressing Wnt3a by lentivirus infection and transplanted them into a COPD rat model. The damage level of COPD rat lung tissue was assessed by pathology analysis and inflammatory cytokines analysis. The engraftment of BMSC was detected by immunofluorescence staining. Statistical analysis was performed using GraphPad Prism 7.

RESULTS

We found that Wnt3a significantly enhanced the engraftment rate of BMSCs in the lungs of rats and further increased their differentiation rate into type II alveolar epithelial cells. We also assessed the expression of inflammatory factors in the lung tissues of COPD rats and discovered that Wnt3a reduced the levels of the inflammatory factors IL-6 and IL-1β while increasing the level of the anti-inflammatory factor IL-10. Our study demonstrates that Wnt3a can improve the engraftment and differentiation rates of BMSCs in the host and further alleviate COPD symptoms by regulating the secretion of inflammatory factors.

CONCLUSION

Constructing BMSCs overexpressing Wnt3a could serve as a new strategy for stem cell therapy in COPD.

摘要

背景

骨髓间充质干细胞（BMSC）疗法是治疗慢性阻塞性肺疾病（COPD）的一种新方法。然而，BMSCs在体内植入困难且易被清除，这阻碍了它们的临床应用。因此，迫切需要探索提高BMSCs在体内植入和分化率的有效方法。

方法

我们通过慢病毒感染构建了过表达Wnt3a的BMSCs，并将其移植到COPD大鼠模型中。通过病理分析和炎性细胞因子分析评估COPD大鼠肺组织的损伤程度。通过免疫荧光染色检测BMSC的植入情况。使用GraphPad Prism 7进行统计分析。

结果

我们发现Wnt3a显著提高了BMSCs在大鼠肺中的植入率，并进一步提高了它们向II型肺泡上皮细胞的分化率。我们还评估了COPD大鼠肺组织中炎性因子的表达，发现Wnt3a降低了炎性因子IL-6和IL-1β的水平，同时提高了抗炎因子IL-10的水平。我们的研究表明，Wnt3a可以提高BMSCs在宿主体内的植入和分化率，并通过调节炎性因子的分泌进一步减轻COPD症状。