Bone marrow mesenchymal stem cell transplantation alleviates radiation-induced myocardial fibrosis through inhibition of the TGF-β1/Smad2/3 signaling pathway in rabbit model

Jian Jun Gu; Hong Xiao Li; Wei Wei; Xiao Lin Sun; Bi Chun Li; Yong Chen; Jun Li; Xiang Gu

doi:10.1016/j.reth.2023.04.003

Bone marrow mesenchymal stem cell transplantation alleviates radiation-induced myocardial fibrosis through inhibition of the TGF-β1/Smad2/3 signaling pathway in rabbit model

Regen Ther. 2023 May 29:24:1-10. doi: 10.1016/j.reth.2023.04.003. eCollection 2023 Dec.

Authors

Jian Jun Gu^{1

2}, Hong Xiao Li², Wei Wei^{1

2}, Xiao Lin Sun^{1

2}, Bi Chun Li³, Yong Chen⁴, Jun Li⁵, Xiang Gu²

Affiliations

¹ Department of Cardiology, Institute of Translational Medicine, Medical College, Yangzhou University, PR China.
² Department of Cardiology, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, PR China.
³ Key Laboratory of Animal Breeding and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, 225001, PR China.
⁴ Department of Ultrasound, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, PR China.
⁵ Department of Radiology, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, PR China.

Abstract

Background: and purpose: Radiotherapy (RT) is an effective treatment for most malignant chest tumors. However, radiation-induced myocardial fibrosis (RIMF) is a serious side effect of RT. Currently, due to the mechanism of RIMF has not been fully elucidated, there is a lack of effective therapeutic approach. In this study, we aimed to investigate the role and possible mechanisms of bone marrow mesenchymal stem cells (BMSCs) in the therapy of RIMF.

Materials and methods: Twenty-four New Zealand white rabbits were allotted into four groups (n = 6). Rabbits in the Control group received neither irradiation nor treatment. A single dose of 20 Gy heart X-irradiation was applied to the RT group, RT + PBS group and RT + BMSCs group. Rabbits in the RT + PBS group and RT + BMSCs group were injected with 200 μL PBS or 2 × 10⁶ cells via pericardium puncture 24 h following irradiation, respectively. Echocardiography was used to test the cardiac function; Then the heart samples were collected, and processed for histopathological, Western blot and immunohistochemistry investigations.

Results: It was observed that BMSCs have therapeutic effect on RIMF. Compared with the Control group, inflammatory mediators, oxidative stress and apoptosis were significantly increased, meanwhile, cardiac function was remarkably decreased in the RT group and RT + PBS group. However, in the BMSCs group, BMSCs significantly improved cardiac function, decreased inflammatory mediators, oxidative stress and apoptosis. Furthermore, BMSCs remarkably reduced the expression level of TGF-β1 and the phosphorylated-Smad2/3.

Conclusions: In conclusion, our research indicates BMSCs have the potential to alleviate RIMF through TGF-β1/Smad2/3 and would be a new therapeutic approach for patients with myocardial fibrosis.

Keywords: BMSCs; Cardiac function; RIMF; Smad2/3; TGF-β1.