Endothelial cell protection in xenotransplantation: looking after a key player in rejection

Abstract

The endothelium, as an organ at the interface between the intra- and extravascular space, actively participates in maintaining an anti-inflammatory and anti-coagulant environment under physiological conditions. Severe humoral as well as cellular rejection responses, which accompany cross-species transplantation of vascularized organs as well as ischemia/reperfusion injury, primarily target the endothelium and disrupt this delicate balance. Activation of pro-inflammatory and pro-coagulant pathways often lead to irreversible injury not only of the endothelial layer but also of the entire graft, with ensuing rejection. This review focuses on strategies targeted at protecting the endothelium from such damaging effects, ranging from genetic manipulation of the donor organ to soluble, as well as membrane-targeted, protective strategies.

Pre‐treatment of porcine pulmonary xenograft with desmopressin: a novel strategy to attenuate platelet activation and systemic intravascular coagulation in an ex‐vivo model of swine‐to‐human pulmonary xenotransplantation

“…Following exposure to human blood, porcine endothelial cells are activated possibly by multiple stimuli, such as ischemic or mechanical injury, and binding of xenoreactive antibodies with or without subsequent complement activation, leading to exposure of pro-coagulant and proinflammatory surfaces and expression or secretion of P-selectin, vWF, and platelet-activating factor [14][15][16]. Porcine vWF binds to human platelets and induces their activation and aggregation [17].…”

Achieving the ideal properties for vascular bypass grafts using a tissue engineered approach: a review

“…Biologically sourced scaffolds can be seeded with variable ease, with autologous structures seeding readily compared with decellularized xenografts, especially if the latter have not been adequately treated, resulting in residual antigenicity [4].…”

“…This has translated clinically into poor medium-to long-term patency of synthetic grafts when used in low flow states and small calibre (<6 mm) bypass. The 5 year primary patency of PTFE grafts which cross the knee joint is less than 30% [4], resulting in considerable re-interventions and limb loss. Therefore in cardiovascular bypass surgery, when small calibre conduits are required, every effort is made to use autologous vessels.…”

Xenotransplantation Literature Update January–February, 2006

“…During the period January to February 2006, five reviews on xenotransplantation were published [1][2][3][4][5].…”

“…Banz and Rieben [4] reviewed the importance of vascular endothelium in the rejection process of xenotransplanted organs and analyzed different strategies to protect endothelium from injury related to the activation of pro-inflammatory and pro-coagulant pathways.…”