Toward beta cell replacement for diabetes

EMBO J. 2015 Apr 1;34(7):841-55. doi: 10.15252/embj.201490685. Epub 2015 Mar 1.

Abstract

The discovery of insulin more than 90 years ago introduced a life-saving treatment for patients with type 1 diabetes, and since then, significant progress has been made in clinical care for all forms of diabetes. However, no method of insulin delivery matches the ability of the human pancreas to reliably and automatically maintain glucose levels within a tight range. Transplantation of human islets or of an intact pancreas can in principle cure diabetes, but this approach is generally reserved for cases with simultaneous transplantation of a kidney, where immunosuppression is already a requirement. Recent advances in cell reprogramming and beta cell differentiation now allow the generation of personalized stem cells, providing an unlimited source of beta cells for research and for developing autologous cell therapies. In this review, we will discuss the utility of stem cell-derived beta cells to investigate the mechanisms of beta cell failure in diabetes, and the challenges to develop beta cell replacement therapies. These challenges include appropriate quality controls of the cells being used, the ability to generate beta cell grafts of stable cellular composition, and in the case of type 1 diabetes, protecting implanted cells from autoimmune destruction without compromising other aspects of the immune system or the functionality of the graft. Such novel treatments will need to match or exceed the relative safety and efficacy of available care for diabetes.

Keywords: beta cells; cell replacement therapy; stem cells; type 1 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Autografts
  • Cellular Reprogramming / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy
  • Humans
  • Immunosuppression Therapy*
  • Insulin-Secreting Cells* / immunology
  • Insulin-Secreting Cells* / transplantation
  • Islets of Langerhans Transplantation / immunology*
  • Kidney Transplantation
  • Transplantation Immunology*