Toward a cure for diabetes: iPSC and ESC-derived islet cell transplantation trials

Abstract

Advancements in regenerative medicine, particularly through the use of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), are garnering substantial attention as potential solutions to the limited availability of donors, leading to prolonged waiting periods for people with type 1 diabetes who require transplantation of pancreatic islets from deceased donors. The promising outcomes from recent clinical trials suggest that transplantation of iPSC- or ESC-derived islet cells could pave the way for more effective and broadly accessible treatment options. This progress holds potential not only for individuals with type 1 diabetes but may also extend to type 2 diabetes treatment in the future.

Figure 1

Islet cell transplantation: Methodologies and challenges to overcome. Transplantation of pancreatic islets from deceased donors presents a promising treatment avenue aimed at restoring physiological insulin secretion by re‐establishing pancreatic β‐cell function, primarily for patients with type 1 diabetes. Despite its potential, several significant challenges persist. These include the limited availability of donors, leading to prolonged waiting periods for patients in need (1), the necessity for multiple transplantations to achieve satisfactory outcomes (2), and the risk of side effects from immunosuppressive therapy (3). Advancements in regenerative medicine, particularly through the use of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), are garnering substantial attention as potential solutions to these challenges. Clinical trials exploring the safety and efficacy of intraportal islet transplantation using ESC‐derived islet cells, as well as subcutaneous islet transplantation using ESC‐derived or patient‐specific iPSC‐derived islet cells, with or without encapsulation devices, have shown promising initial results. Nonetheless, significant obstacles remain. These include potential adverse effects from immunosuppressive agents (3) and the high cost and lengthy preparation time associated with patient‐specific iPSC‐derived islet cells (4). To address these barriers, ongoing research focuses on the development of genetically modified ESC‐ or iPSC‐derived islet cells with immune evasion properties, as well as the creation of more efficient, cost‐effective protocols for the differentiation and expansion of these cells. The promising outcomes from recent clinical trials suggest that transplantation of iPSC‐ or ESC‐derived islet cells could pave the way for more effective and broadly accessible treatment options. This progress holds potential not only for individuals with type 1 diabetes but may also extend to type 2 diabetes treatment in the future.