Emerging routes to the generation of functional β-cells for diabetes mellitus cell therapy

Abstract

Diabetes mellitus, which affects more than 463 million people globally, is caused by the autoimmune ablation or functional loss of insulin-producing β-cells, and prevalence is projected to continue rising over the next decades. Generating β-cells to mitigate the aberrant glucose homeostasis manifested in the disease has remained elusive. Substantial advances have been made in producing mature β-cells from human pluripotent stem cells that respond appropriately to dynamic changes in glucose concentrations in vitro and rapidly function in vivo following transplantation in mice. Other potential avenues to produce functional β-cells include: transdifferentiation of closely related cell types (for example, other pancreatic islet cells such as α-cells, or other cells derived from endoderm); the engineering of nonβ-cells that are capable of modulating blood sugar; and the construction of synthetic 'cells' or particles mimicking functional aspects of β-cells. This Review focuses on the current status of generating β-cells via these diverse routes, highlighting the unique advantages and challenges of each approach. Given the remarkable progress in this field, scalable bioengineering processes are also discussed for the realization of the therapeutic potential of derived β-cells.

The Role of Circulating RBP4 in the Type 2 Diabetes Patients with Kidney Diseases: A Systematic Review and Meta-Analysis

“…Diabetes mellitus (DM) affects more than 463 million people globally, and this number is supposed to increase to 700 million by 2045 [ 1 ]. Diabetic nephropathy (DN) is a common and serious complication of DM [ 2 ] and is one of the leading causes of end-stage renal disease (ESRD) worldwide [ 3 ].…”

Pluripotent stem cell SOX9 and INS reporters facilitate differentiation into insulin-producing cells

“…3D differentiation in shaking orbital cultures or small bioreactors has become the standard for many somatic cell types [31][32][33]. Transition from 2D to 3D alone, without changes in extrinsic or other factors, can lead to a considerable phenotypic improvement [34].…”

Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress

“…Insulin application and blood glucose control is the standard therapeutic methods for type 1 diabetes. However, adverse effects are accompanied by intense insulin injection, and maintaining normal glycemic levels is often difficult and associated with increased frequency of hypoglycemic episodes, prompting new strategies to tackle this emerging global epidemic [219,220]. It has been demonstrated that MSCs could differentiate into glucose competent pancreatic insulin-producing cells (IPCs) in vitro as well as in vivo [221][222][223], in addition to the capacity to regulate the immunomodulatory effects.…”