The novel compound PICCS improves cell viability during cold storage and reduces pulmonary ischemia-reperfusion injury in a rat model

Abstract

Abstract A simple method to achieve better organ preservation is the addition of compounds to the preservation solution, which effectively inhibits cold injury. We aimed to develop novel compounds for better lung graft preservation using TY52156 as a seed compound, which reportedly inhibits cold injury of vascular endothelial cells and exerts organ-protective effects in a rat heart transplant model. Eighteen compounds were newly synthesized and screened using an in vitro screening system for cold storage and rewarming. Among them, three of the synthesized compounds increased cell viability after 4 days of cold storage in both vascular endothelial and airway epithelial cells without cytotoxic effects. They were denoted as preventing inducible cell damage in cold stress (PICCS)-1, -2, and -3. PICCS-3 inhibited apoptotic signaling in airway epithelial cells after 6 h of cold storage. In a rat lung transplant ischemia-reperfusion injury (IRI) model, addition of PICCS-3 to the organ preservation solution attenuated IRI, as evidenced by improved physiological data of the lung graft, reduced lung edema, and extravasation of neutrophils. This study demonstrates the potential of a structure-based synthetic approach and an in vitro screening system using appropriate cell types to develop novel effective additives for organ preservation solutions.

Keywords

• Organ preservation
• Ischemia-reperfusion injury
• Cell death
• PICCS