Mechanisms and consequences of injury and repair in older organ transplants

Abstract

Donor organ scarcity remains a significant clinical challenge in transplantation. Older organs, increasingly utilized to meet the growing demand for donor organs, have been linked to inferior transplant outcomes. Susceptibility to organ injury, reduced repair capacity, and increased immunogenicity are interrelated and impacted by physiological and pathological aging processes. Insights into the underlying mechanisms are needed to develop age-specific interventional strategies with regards to organ preservation, immunosuppression, and allocation. In this overview, we summarize current knowledge of injury and repair mechanisms and the effects of aging relevant to transplantation.

Figure 1

Organ age contributes to an augmented susceptibility to injury and to an impaired repair and regenerative capacity. Recipient immune responses are augmented subsequent to an inflammatory environment of the donor organ, increased antigenic burden, epigenetic DNA alterations and an enhanced antigen presentation by resident dendritic cells. Additionally, the old organ is more prone to acute injuries such as ischemia reperfusion injury. Degenerative processes of the organ such as reduced functional mass, vasculopathies, steatosis and fibrosis advance the injury furthermore, while impaired cellular stress responses and diminished growth signaling and receptor responsiveness debilitate repair function.