Beta-cell replacement therapy

Abstract

Purpose of reviewThis article provides a summary of the current outcomes of b-cell replacement strategies, an algorithm for choosing a specific modality while highlighting associated advantages and disadvantages, and outlines remaining challenges and areas of active investigation in b-cell replacement therapy. Recent findingsThe most recent reports of islet cell allotransplantation have shown improvements over previous eras and now rival some outcomes of pancreas alone transplantation. Active areas of investigation are focused on improving techniques for islet isolation, graft monitoring, and managing challenges posed by the innate and alloimmune systems. SummaryPatients with insulin-dependent diabetes who continue to experience life threatening hypoglycemia despite maximal medical management can benefit from b-cell replacement. Emerging nontransplant technologies have not provided a physiologic euglycemic state to the extent offered by transplantation. Islet transplantation eliminates hypoglycemic episodes/unawareness, facilitates normalization of hemoglobin A1c (HbA1c), decreases microvascular disease progression, and improves quality of life for patients with problematic diabetes. Mid-and long-term outcomes of islet transplantation performed at expert centers approximate those of registry reports of solitary pancreas transplant, whereas the complication profile is quite favorable.

Stepwise Approach to Problematic Hypoglycemia in Korea: Educational, Technological, and Transplant Interventions

“…The proportion of patients with insulin independence after allogeneic pancreas and islet transplantation is around 70% and 25% to 50%, respectively [18192021]. However, recent international cohort studies have reported that the proportion of recipients with fasting C-peptide levels of >0.3 ng/mL, corresponding to optimal glycemic control without severe hypoglycemia, was approximately 70% at 5 years after allogeneic islet transplantation, which is similar to the results found after pancreas transplantation [1920].…”

Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet Functional Potency and Islet Transplantation Outcomes

“… 42 However, the widespread success of islet transplantation has been limited by the need for multiple donor pancreata and repeated islet infusions to achieve insulin independence in recipients. 43 Despite progressive refinement of the technique, islet transplantation is still limited by the supply of high-quality transplantable organs, and institutions and clinicians are turning to the use of lower quality expanded criteria donor (ECD) organs in an attempt to meet an ever-growing demand to increase the donor pool. 44 Cadaveric organs present a significant challenge to successful long-term graft function when compared to organs recovered form living donors.…”

Is islet transplantation a realistic approach to curing diabetes?

“…In chronic pancreatitis with intractable abdominal pain, IAT after total pancreatectomy is already a standard therapy in available centers [9]. In this setting, a modest islet mass, typically a dose of 5,000 islet equivalents (IE)/kg, can secure complete or partial islet graft function, as defined by the use of only long-acting basal insulin and an HbA1c of < 7%, in 68% of patients at 5 years and in 57% at 10 years post-transplant, although an immediate blood-mediated inflammatory reaction is still a concern [4]. …”