Single-donor islet transplantation in type 1 diabetes: patient selection and special considerations

Abstract

Type 1 diabetes mellitus is an autoimmune disorder of the endocrine pancreas that currently affects millions of people in the United States. Although the disease can be managed with exogenous insulin administration, the ultimate cure for the condition lies in restoring a patient’s ability to produce their own insulin. Islet cell allotransplantation provides a means of endogenous insulin production. Though far from perfected, islet transplants are now a proven treatment for type 1 diabetics. However, proper patient selection is critical for achieving optimal outcomes. Given the shortage of transplantable organs, selecting appropriate candidates for whom the procedure will be of greatest benefit is essential. Although many of those who receive islets do not retain insulin independence, grafts do play a significant role in preventing hypoglycemic episodes that can be quite detrimental to quality of life and potentially fatal. Additionally, islet transplant requires lifelong immunosuppression. Antibodies, both preformed and following islet infusion, may play important roles in graft outcomes. Finally, no procedure is without inherent risk and islet transfusions can have serious consequences for recipients’ livers in the form of both vascular and metabolic complications. Therefore, patient-specific factors that should be taken into account before islet transplantation include aims of therapy, sensitization, and potential increased risk for hepatic and portal-venous sequelae.

Modulation of Inflammatory Cytokines and Islet Morphology as Therapeutic Mechanisms of Basella alba in Streptozotocin-Induced Diabetic Rats

“…This may be a partial result of the unchallenged action of Ba in the stimulation of islet cell proliferation. Presently, the curative therapies of T1DM are based on the restoration of endogenous insulin production either by the transplantation of beta-islet cells or the whole pancreas with concurrent immunosuppression ( 28 , 29 ). This has its own disadvantages, especially those that stem from the continuous need to suppress the immune system and the increased risk of vascular and metabolic complications ( 29 ).…”

“…Presently, the curative therapies of T1DM are based on the restoration of endogenous insulin production either by the transplantation of beta-islet cells or the whole pancreas with concurrent immunosuppression ( 28 , 29 ). This has its own disadvantages, especially those that stem from the continuous need to suppress the immune system and the increased risk of vascular and metabolic complications ( 29 ). The ability to restart insulin synthesis using a natural medicinal agent that is capable of restoring islet function well enough to achieve better glucose homeostasis in T1DM would therefore be extremely valuable.…”

Immunological aspects of allogeneic pancreatic islet transplantation: a comparison between mouse and human

“…To allow diabetes reversal in patients, generally the infusion of multiple doses of islets is required. These multiple infusions increase the risk of rejection because of HLA mismatches or to donor‐specific alloantibodies . Indeed, the HLA typing, that is essential prior to kidney transplantation, is not compulsory in islet cell transplantation.…”

Regulation of Inflammatory Response in Islet Transplantation

“…Multiple islet infusion are high risk factors for increased de novo DSA, which is associated with graft failure [100,101]. A recent study reported that 5/16 islet transplant recipients (31%) developed de novo DSA against mismatched donor HLA: three recipients post-first transplant; two recipients post-second transplant [102].…”

“…It is suggested that the reasons might relate to the low DSA titres, inability to activate the complement and the lack of allogenic endothelial targets in islet graft [103]. Alloimmune rejection remains a significant obstacle of successful islet transplant and further study will be required to characterize optimal patient-donor matching characteristics [101].…”