Role of Whole Organ Pancreas Transplantation in the Day of Bioartificial and Artificial Pancreas

Abstract

While exogenous insulin administration remains the cornerstone of management for type I diabetes mellitus (T1DM), patients now have a variety of options that include whole organ pancreas transplant, islet cell transplant, extracorporeal mechanical (bihormonal artificial pancreas), and implanted bioartificial (encapsulated islet) delivery systems. The purpose of this review is to compare these options and consider future developments. Use of whole organ pancreas transplant has declined in the USA over the past several years. Pancreas transplant offers the most durable form of beta cell replacement, especially in the context of a simultaneous kidney-pancreas transplant or a pancreas after kidney transplant. However, pancreatic transplant is associated with significant perioperative morbidity including the risk of a leak of exocrine secretions. Despite a decline in popularity, pancreas transplant outcomes remain excellent. Pancreatic islet transplant offers the opportunity for beta cell replacement with less morbidity. Islet cell transplant outcomes have improved requiring fewer donor pancreata to achieve insulin independence. However, islet cell recipients continue to incur the risk of lifelong immunosuppression, and, to date, long-term islet cell transplant outcomes are not equal to whole organ transplant. Mechanical solutions have progressed significantly, as technology as enable continuous glucose monitoring and bihormonal (insulin and glucagon) pumps. This technology is limited by the sensitivity of the glucose monitor and the time to effective absorption and distribution of subcutaneous administration of hormones. Finally, bioartificial encapsulated islets are in early clinical trials. Encapsulation results in an immune privileged environment eliminating the need for immunosuppression. However, long-term survival of the islets in vivo has not been established, and other barriers (e.g., fibrin deposition occluding the pores of the encapsulated islet) remain to be overcome. The optimal therapeutic choice for patients with type 1 diabetes must be personalized for the patient and address their specific comorbid conditions (specifically concomitant renal failure), surgical risk, and medical literacy. Increase options promise the opportunity for better glucose control and further reduction in secondary diabetic complications.