Cell Therapy for Type 1 Diabetes: From Islet Transplantation to Stem Cells

Abstract

Background. The field of cell therapy of type 1 diabetes is a particularly interesting example in the scenario of regenerative medicine. In fact, β cell replacement has its roots in the experience of islet transplantation, which began 40 years ago, and is currently a rapidly accelerating field, with several ongoing clinical trials using β cells derived from stem cells. Summary. Type 1 diabetes is particularly suitable for cell therapy as it is a disease due to the deficiency of only one cell type, the insulin-producing β cell, and this endocrine cell does not need to be positioned inside the pancreas to perform its function. On the other hand, the presence of a double immunological barrier, the allogeneic one and the autoimmune one, make the protection of β cells from rejection a major challenge. Until today, islet transplantation has taught us a lot, pioneering immunosuppressive therapies, graft encapsulation, tissue engineering, test of different implant sites and has stimulated a great variety of studies on β cell function. Nowadays, it is indeed possible to generate functional β cells from the differentiation of pluripotent stem cells and the first pioneering clinical trials with these cells are ongoing. This review starts from islet transplantation, presenting its current indications and the latest published trials to arrive at the prospects of stem cell therapy, presenting the latest innovations in the field. Key messages. The field of β cell replacement is moving forward quickly, especially thanks to all the knowledge generated by the experience of islet transplantation.

A Critical Review of Upcoming New Therapeutic Options in Paediatric Endocrinology

“…The increased risk of diabetic ketoacidosis associated with the use of SGLT2 inhibitors in type 1 diabetes, however, currently precludes its routine use [10]. Finally, cell therapy is perhaps the most promising therapy for the definitive cure of children with type 1 diabetes as illustrated by Sordi et al [11].…”

Advances and challenges of the cell-based therapies among diabetic patients

“…There are currently six registered clinical trials evaluating the use of human pluripotent stem cells for the T1D treatment. All trials except one use PEC-01 cells, which consist of a mixture of pancreatic endoderm and polyhormonal cell population derived from CyT49 stem cells that are fully committed to endocrine differentiation upon implantation [ 149 ]. The initial trial implanted PEC-01 cells within an encapsulation device, hypothesizing no need for immunosuppression.…”

“…Preliminary results suggest early engraftment and insulin secretion. The manin challenge was controlling immune rejection without systemic immunosuppression [ 149 ]. Several strategies are being explored to address the challenges of immune rejection in stem cell therapies for diabetes.…”