Revisiting the Pathogenesis of Type 1 Diabetes: Importance of Neural Input to Pancreatic Islets and the Therapeutic Capability of Stem Cell Educator TM Therapy to Restore Their Integrity

Abstract

Type 1 diabetes (T1D) is an autoimmune disease with a shortage of islet β cells. To date, the etiology of T1D remains elusive. Increasing clinical evidence and animal studies demonstrate that autoimmune cells are directed against the nervous system of pancreatic islets, contributing to the development of T1D. Therefore, it highlights the necessity to explore novel clinical approaches to fundamentally correct the T1D autoimmunity not only focusing on islet β cells but also on protecting the islet nervous system. This allows the restoration of the integrity of islet innervation and the normal islet β-cell function. To address these issues, we developed a novel technology designated the Stem Cell Educator TM therapy, based on immune education by human cord-blood-derived multipotent stem cells (CB-SC). International amulticenter clinical trials demonstrated its clinical safety and efficacy to treat T1D and other autoimmune diseases. Stem Cell Educator TM therapy may have the potential to revolutionize the treatment of T1D, without the safety and ethical concerns associated with conventional immune and/or stem cell-based therapies.

The functional maturity of grafted human pluripotent stem cell derived-islets (hSC-Islets) evaluated by the glycemic set point during blood glucose normalizing process in diabetic mice

“…The pancreatic islet is innervated by an autonomic axon, and neural input influences its function [ [30] , [31] , [32] ]. Innervation of grafted mouse islets was initiated by 6 weeks and then increased over time [ 33 ], suggesting that the function of grafted-hiPS-islets responds to reinnervation.…”

“…As for innervation, mouse pancreatic endocrine cells are innervated by autonomic nerves in vivo [ [30] , [31] , [32] ], and C57BL/6 mouse pancreatic islets are influenced directly by parasympathetic nerve innervation [ 55 ]. Anatomical studies indicate that human pancreatic endocrine cells are also innervated by autonomic nerves [ 30 ].…”

The Sympathetic‐Immune Milieu in Metabolic Health and Diseases: Insights from Pancreas, Liver, Intestine, and Adipose Tissues

“…Extensive research conducted over the years has emphasized the indispensable role of the nervous system in regulating pancreatic function. [ 2 ] Emerging evidence starts to highlight the significance of its crosstalk with other systems, such as the immune system, in the modulation of pancreatic function and the pathogenesis of pancreatic disorders.…”

“…Overall, the coordinated activity of these neuronal networks ensures the proper function of the pancreas and maintains the delicate balance required for glucose metabolism. [ 2 ]…”