Breaking the limits of experimental pancreas transplantation: Working toward the clinical ideal graft

Abstract

Pancreas transplantation is, at present, the only curative treatment for type-1 diabetes that maintains normoglycemia thus avoiding complications arising from poor glycemic control. Despite its great benefits, the number of pancreas transplants has decreased significantly since its inception in the late 1960s, largely due to demographic changes and the consequent suboptimal quality of donors. The selection criteria for pancreas donors mainly depend on morphological variables such as fatty infiltration, fibrosis, or edema, as well as both functional (amylase and lipase) and clinical variables of the donor. However, the final criterion in the decision-making process is the somewhat subjective assessment of a trained surgeon. That being said, the recent incorporation of graft perfusion machines into clinical practice seems to be changing the work dynamics of the donor organ retrieval team, facilitating decision-making based on objective morphological and functional criteria. Normothermic perfusion using perfusate with supplemental oxygen replicates near physiological parameters thus being a promising strategy for organ preservation. Nevertheless, optimum perfusion parameters are difficult to establish in pancreas transplantation given its complex vascular anatomy combined with an intrinsically low blood flow. The objective of this work is to analyze the results published in the recent literature relating to the considerations of ex-vivo normothermic graft perfusion machines and their usefulness in the field of pancreas transplantation.

Whole-Organ Pancreas and Islets Transplantations in UK: An Overview and Future Directions

“…A systematic review of human and animal's experimental studies showed that ex situ pancreas perfusion reduced ischemic reperfusion injuries, pancreas thrombosis, morbidity of transplantation, and could be a helpful tool to evaluate pancreas prior to transplantation [66]. Normothermic ex situ perfusion with supplemental oxygen replicates near physiological parameters, and seems to be an interesting alternative promising strategy for pancreas organ preservation [68]. However, ideal perfusion parameters are difficult to establish in pancreas transplantation given its complex vascular anatomy and blood flow.…”

European Society for Organ Transplantation (ESOT) Consensus Statement on the Role of Pancreas Machine Perfusion to Increase the Donor Pool for Beta Cell Replacement Therapy

“…In contrast to other solid organs [17], the role of in-situ Normothermic Regional Perfusion after cDCD is emerging whilst ex situ machine perfusion for pancreas and islet transplant is in its infancy. The intrinsic characteristics of the pancreas, with its low blood flow and complex vascular anatomy, makes it highly susceptible to ischemic injury during preservation, resulting in detrimental effects on the organ's microcirculation [18]. This makes the design of the conditions, and the perfusion parameters of machines, more complex than for other solid organs and thus calls for further expert evaluation.…”