Augmenting engraftment of beta cell replacement therapies for T1DM

Abstract

Objectives

For nearly a century, the therapeutic use of exogenous insulin remains the gold standard treatment strategy for patients living with Type 1 Diabetes Mellitus (T1DM). While lifesaving, insulin can fail to prevent the secondary vascular disease and complications inherited with T1DM diagnosis, and for some, this may increase their risk of life-threatening hypoglycemic unawareness. In recent decades transplantation has been demonstrated as the only means (a replacement gold standard therapy) to effectively restore physiologically relevant glycemic control. Moreover, significant advancements in clinical islet transplantation have yielded greater incidences of durable insulin-independence, rescindment of critical hypoglycemia and prevention of comorbidities. Yet, the requisite of life-long immunosuppression and scarcity of a universal and potent cell supply, in addition to the challenges faced with such therapy in vivo, restricts the broad-spectrum application of cell-based therapies.

Key findings

Herein, this review presents the history, current status and persisting challenges confronting cell-based replacement therapies for T1DM. Lastly, we examine modern and future research opportunities designed to enhance the efficacy of cellular transplantation, thereby offering a potential functional cure to all those affected by T1DM.

Conclusions

Given the rapid progress in β-cell replacement therapy, it is hopeful that through multidisciplinary innovations, first-in-human stem cell trials, innocuous immunosuppression and efficacious extrahepatic transplant sites, β-cell replacement therapies will become the cornerstone treatment for the millions worldwide afflicated with T1DM.