Insulitis in Human Type 1 Diabetic Pancreas: From Stem Cell Grafting to Islet Organoids for a Successful Cell-Based Therapy

Abstract

Type 1 diabetes (T1D) is an autoimmune disease with immune cells’ islet infiltration (called “insulitis”), which leads to beta cell loss. Despite being the critical element of T1D occurrence and pathogenesis, insulitis is often present in a limited percentage of islets, also at diagnosis. Therefore, it is needed to define reproducible methods to detect insulitis and beta-cell decline, to allow accurate and early diagnosis and to monitor therapy. However, this goal is still far due to the morphological aspect of islet microvasculature, which is rather dense and rich, and is considerably rearranged during insulitis. More studies on microvasculature are required to understand if contrast-enhanced ultrasound sonography measurements of pancreatic blood-flow dynamics may provide a clinically deployable predictive marker to predict disease progression and therapeutic reversal in pre-symptomatic T1D patients. Therefore, it is needed to clarify the relation between insulitis and the dynamics of β cell loss and with coexisting mechanisms of dysfunction, according to clinical stage, as well as the micro vessels’ dynamics and microvasculature reorganization. Moreover, the ideal cell-based therapy of T1D should start from an early diagnosis allowing a sufficient isolation of specific Procr+ progenitors, followed by the generation and expansion of islet organoids, which could be transplanted coupled to an immune-regulatory therapy which will permit the maintenance of pancreatic islets and an effective and long-lasting insulitis reversal.

An updated algorithm for an effective choice of continuous glucose monitoring for people with insulin-treated diabetes

“…CGM contributes to improve the lives and health of PwD. On the basis of the growing evidence, its use is currently recognized as the standard of care for people with type 1 diabetes and for a subset of those with insulin-requiring type 2 diabetes [ 1 , 2 , 48 ].…”

Antidiabetic Properties of <i>Bidens pilosa</i> and Its Polyacetylenic Compounds for Management of Diabetes: Systematic Review

“…Diabetes mellitus is disease that results from the impairment of either the secretion or action of insulin in the body and characterized by metabolism of aberrant protein, lipids and glucose [28] [46]. Type 1 diabetes is a disease that results from the destruction of insulin producing pancreatic β-cells by immune cells that exhibit a strong autoimmune reaction [47] shown in both db/db and NOD mice which are both animal models for diabetes [28] [29] [58]. Glycemic control in type 1 diabetes by B. pilosa and its polyacetylenic compounds is achieved through T-cell regulation, long-term therapeutic action and through increased insulin expression and protection of pancreatic β-cells in type 2 diabetes [32].…”

Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy

“…Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes [ 1 , 2 ] and has been a major cause of end-stage renal disease (ESRD) in patients [ 3 ]. Currently, effective therapeutic strategies to counteract and reverse the progression of DN are lacking.…”