Regulated cell death in organ transplantation: recent developments and mechanistic overview

Organ transplantation is a definitive therapeutic option for patients with end-stage organ dysfunction and failure. Ischaemia-reperfusion (IR) injury is one of the leading causes of low graft utilization as it significantly increases the risk of primary graft dysfunction and acute rejection following transplantation. This risk is particularly high for organs obtained from donation after circulatory death (DCD) when compared with the organs from donation after brain death (DBD). IR injury exacerbates tissue damage via various mechanisms including the induction of regulated cell death. Regulated cell death and its consequences play critical roles in determining graft survival and function, thereby influencing the overall success of the transplant. Understanding the mechanisms underlying regulated cell death in IR injury is essential for developing therapeutic strategies to minimize tissue damage and improve clinical outcomes in organ transplantation. This review mainly discusses different types of regulated cell death and underlying mechanisms towards preventive cell death strategies in DBD and DCD organ transplantation in preclinical settings.