Ex vivo MFG-E8 treatment improves the function of lungs procured from cardiac death donors in preclinical porcine model

Ping Li; Kai Peng; Li Gang Liu; Qing Yun Liu; Zhen Hua Huang; Durgahee Mouniir Sha Ahmad; Xiang Wei; Si Hai Gao

doi:10.1016/j.heliyon.2024.e33614

Ex vivo MFG-E8 treatment improves the function of lungs procured from cardiac death donors in preclinical porcine model

Heliyon. 2024 Jun 25;10(13):e33614. doi: 10.1016/j.heliyon.2024.e33614. eCollection 2024 Jul 15.

Authors

Ping Li^{1

2

3}, Kai Peng^{1

2}, Li Gang Liu^{1

2}, Qing Yun Liu^{1

2}, Zhen Hua Huang^{1

2}, Durgahee Mouniir Sha Ahmad^{1

2}, Xiang Wei^{1

2}, Si Hai Gao^{1

2}

Affiliations

¹ Department of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
² Key Laboratory of Organ Transplantation, Chinese Ministry of Education and Chinese Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
³ Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.

Abstract

Ex vivo lung perfusion (EVLP) is a promising technology that allows the re-evaluation of donor lungs and has the potential to improve marginal lung reconditioning. The present study focused on the effects of milk fat globule epidermal growth factor 8 (MFG-E8) on the function of donation after circulatory death (DCD) lungs during EVLP and transplant reperfusion. Domestic swine were assigned to 4 groups. In the control group, the donor lungs lacking warm ischemia were preserved in Perfadex for 4 h. The swine in the other three groups underwent hypoxic arrest, followed by 1 h of warm ischemia. The DCD lungs were procured and randomly divided into three groups: cold static preservation (DCD-CSP) group, DCD-EVLP group, and DCD-MFG-E8 group. The left lung of all groups was transplanted and reperfused. During EVLP and reperfusion, lung functions and pathological evaluations were performed. Treatment with MFG-E8 resulted in significantly improved blood oxygenation. The mean pulmonary artery pressure, peak airway pressure, and expression of IL-1β, IL-6, and IL-12 were significantly lower but IL-10 was higher in the DCD -MFG-E8 group. Furthermore, the lung injury severity score, pulmonary edema, and wet-to-dry weight ratio were also reduced in MFG-E8-treated lungs. However, the pulmonary vascular resistance and expression of TNF-α did not differ from the DCD -EVLP group but were significantly lower than in the DCD -CSP group. Adding MFG-E8 into the perfusate during EVLP obtains optimal graft function of lungs from DCD. This finding, if confirmed clinically, can be applied to recondition grafts and expanded use of DCD lungs.

Keywords: EVLP; Lung transplantation; MFG-E8; Marginal donor lungs.