Toward beta cell replacement for diabetes.
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.
The New York Stem Cell Foundation Research Institute, New York, NY, USA.
Bjarki
B
Johannesson
Naomi Berrie Diabetes Center & Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Lina
L
Sui
The New York Stem Cell Foundation Research Institute, New York, NY, USA.
Donald O
DO
Freytes
Columbia Center for Translational Immunology, Department of Medicine and Naomi Berrie Diabetes Center, Columbia University, New York, NY, USA.
Remi J
RJ
Creusot
The New York Stem Cell Foundation Research Institute, New York, NY, USA Naomi Berrie Diabetes Center & Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA de2220@cumc.columbia.edu.
Dieter
D
Egli
D000818:Animals; D064592:Autografts; D065150:Cellular Reprogramming / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D007165:Immunosuppression Therapy; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000637:transplantation; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D016030:Kidney Transplantation; D014181:Transplantation Immunology
beta cells; cell replacement therapy; stem cells; type 1 diabetes