Lessons from Human Islet Transplantation Inform Stem Cell-Based Approaches in the Treatment of Diabetes

• Published in: Frontiers in endocrinology (Lausanne) Vol. 12; p. 636824
• Main Authors: Triolo, Taylor M, Bellin, Melena D
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 11-03-2021
• Subjects: allotransplantation; Blood Glucose - metabolism; Cell Differentiation; Diabetes Mellitus - therapy; diabetes treatment; Embryonic Stem Cells - metabolism; Endocrinology; Humans; Hyperglycemia - metabolism; Hypoglycemia - metabolism; Immune System; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - cytology; islet transplantation; Islets of Langerhans Transplantation; Pancreas - metabolism; Pluripotent Stem Cells - cytology; Risk; Stem Cells - cytology; total pancreatectomy with islet autotransplant (TPIAT); Transplantation, Homologous; type 1 diabetes; type 2 diabetes; type 1 diabetes; stem cell differentiation; type 2 diabetes; beta cell transplantation; total pancreatectomy with islet autotransplant (TPIAT); islet transplantation; allotransplantation; diabetes treatment
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2021.636824

Diabetes mellitus is characterized by the body's inability to control blood glucose levels within a physiological range due to loss and/or dysfunction of insulin producing beta cells. Progressive beta cell loss leads to hyperglycemia and if untreated can lead to severe complications and/or death. Treatments at this time are limited to pharmacologic therapies, including exogenous insulin or oral/injectable agents that improve insulin sensitivity or augment endogenous insulin secretion. Cell transplantation can restore physiologic endogenous insulin production and minimize hyper- and hypoglycemic excursions. Islet isolation procedures and management of transplant recipients have advanced over the last several decades; both tight glycemic control and insulin independence are achievable. Research has been conducted in isolating islets, monitoring islet function, and mitigating the immune response. However, this procedure is still only performed in a small minority of patients. One major barrier is the scarcity of human pancreatic islet donors, variation in donor pancreas quality, and variability in islet isolation success. Advances have been made in generation of glucose responsive human stem cell derived beta cells (sBCs) and islets from human pluripotent stem cells using directed differentiation. This is an emerging promising treatment for patients with diabetes because they could potentially serve as an unlimited source of functional, glucose-responsive beta cells. Challenges exist in their generation including long term survival of grafts, safety of transplantation, and protection from the immune response. This review focuses on the progress made in islet allo- and auto transplantation and how these advances may be extrapolated to the sBC context.