Therapies for Type 1 Diabetes: Current Scenario and Future Perspectives

Abstract

Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing β cells located in the endocrine pancreas in areas known as islets of Langerhans. The current standard-of-care for T1D is exogenous insulin replacement therapy. Recent developments in this field include the hybrid closed-loop system for regulated insulin delivery and long-acting insulins. Clinical studies on prediction and prevention of diabetes-associated complications have demonstrated the importance of early treatment and glucose control for reducing the risk of developing diabetic complications. Transplantation of primary islets offers an effective approach for treating patients with T1D. However, this strategy is hampered by challenges such as the limited availability of islets, extensive death of islet cells, and poor vascular engraftment of islets post-transplantation. Accordingly, there are considerable efforts currently underway for enhancing islet transplantation efficiency by harnessing the beneficial actions of stem cells. This review will provide an overview of currently available therapeutic options for T1D, and discuss the growing evidence that supports the use of stem cell approaches to enhance therapeutic outcomes.

Keywords: Type 1 diabetes; endothelial colony forming cells; immune therapies; induced pluripotent stem cells; insulin therapy; islet transplant; mesenchymal stem cells.

Figure 1.

Procedure for human pancreatic islet isolation from a donor and transplantation into the recipient: Donor pancreas are harvested and preserved in a temperature regulated preservation chamber prior to collagenase digestion in a Ricordi chamber. The chamber consists of silicon beads that are constantly agitated and perfused with the perfusion solution via a peristaltic pump. The digested islets are collected and purified using density gradient centrifugation. Prior to transplantation into the recipient, the islets are cultured in in vitro to assess viability and insulin secretion.

Figure 2.

Sources of progenitor/stem cells: Mesenchymal stem cells also known as adult stem cells are highly multipotent and are known to differentiate into several specialised cells, including the vascular pericytes. Studies have suggested adipocytes and the bone marrow as an efficient source of MSCs, and remain attractive option for allogenic MSC co-transplantation with islets. Endothelial colony forming cells are vascular stem cells isolated from mononuclear fraction of umbilical cord blood. While somatic cells can be programmed to generate iPSCs, human blastocyst is the source of hESCs. ECFCs indicate endothelial colony forming cells; hESCs, human embryonic stem cells; iPSCs, induced pluripotent stem cells; MSCs, mesenchymal stem cells.

Figure 3.

Future strategies for successful outcome of human islet transplantation: While the pre-transplant islet isolation stages have been carefully optimised, there is more than 1 strategy to enhance the efficiency, viability, and biological function of the transplanted islets. Once purified islets are cultured in vitro, they can be co-transplanted with recipient’s own stem cells to enhance vascularisation, overcoming islet graft loss, and dysfunction post-transplantation. Another strategy is to use transgenic neonatal pigs as a source of islets. The overall survival during the pre-transplant period and post-transplant function of purified islets can be further enhanced using encapsulation strategies either alone or in combination with conventional therapies.