New insights into ischemia-reperfusion injury signaling pathways in organ transplantation

Abstract

Purpose of reviewIschemia-reperfusion injury (IRI) leading to allograft rejection in solid organ transplant recipients is a devastating event that compromises graft and patient survival. As our clinical knowledge regarding its definition and presentation has significantly improved over the last years, adequate biomarkers translating to important therapeutic intervention remains a challenge. This review will summarize recent findings in this area.Recent findingsIn the past 18 months, our understanding of organ transplantation IRI has improved. IRI involves a positive amplification feedback loop encompassing damaged cells at the graft site, the activity of redox-sensitive damage-associated molecular patterns, and local sequestration of recipient-derived monocytes, lymphocytes and polymorphonuclear leukocytes, like neutrophils, to sustain the immunological cascade and to enhance the destruction of the foreign tissue. Recent studies have identified critical components leading to IRI, including the oxidation state of high mobility group box 1, a classic danger signal, its role in the Toll-like receptor 4–interleukin (IL)-23–IL-17A signaling axis, and the role of neutrophils and CD321, a marker for transmigration of circulating leukocytes into the inflamed tissue. In addition, recent findings imply that the protective functions mediated by autophagy activation counterbalance the detrimental nucleotide-binding domain-like receptor family, pyrin domain containing 3 inflammasome pathway. Finally, clinical studies reveal the posttransplant variables associated with early allograft dysfunction and IRI.SummaryThe future challenge will be understanding how crosstalk at the molecular and cellular levels integrate prospectively to predict which peri-transplant signals are essential for long-term clinical outcomes.

Si-based agent alleviated small bowel ischemia–reperfusion injury through antioxidant effects

“…Because organ transplantations, such as those of the lungs, heart, and kidneys, are closely related to IR injury, the success rate of transplantation depends on the extent to which IR injury is suppressed 33 , 34 . According to previous reports, the administration of hydrogen gas has been proven effective in suppressing IR injury after liver and lung transplantation 35 , 36 , and hydrogen is very effective for successful organ transplantation 37 , 38 .…”

Lipid droplets, autophagy, and ER stress as key (survival) pathways during ischemia‐reperfusion of transplanted grafts

“…Clinical research on ERS, autophagy, and LD in the context of IRI in transplantation is relatively specialized and still developing. Although there is significant interest in these mechanisms at the basic science and experimental level, the number of clinical studies directly focusing on these aspects in transplantation is limited (Dery et al, 2023). Many of these studies are still early and often focus on understanding molecular and cellular mechanisms rather than direct clinical applications.…”

The Future Is Now: OrganEx Technology and Its Implications for Transplant Medicine

“…The Future Is Now: OrganEx Technology and Its Implications for Transplant Medicine Sergio Duarte, PhD, 1 Anne-Marie Carpenter, MD, 1 and Ali Zarrinpar, MD, PhD 1 T he function of donor organs after transplantation depends on the quality of procurement and preservation. The absence of oxygen and nutrients damages tissues, swiftly triggering cell death and impairing viability and function.…”

“…More injury occurs at reperfusion, when reestablishment of circulation triggers a sterile immunologic cascade, further destroying tissues. 1 The transition from physiological circulation to organ explantation in living donation and donation after brain death is usually controlled with hypothermic solutions. Organs procured from donors after circulatory death (DCDs) are prone to more extensive injury.…”