β-Cell Replacement Strategies: The Increasing Need for a “β-Cell Dogma”

Abstract

Type 1 diabetes is an auto-immune disease resulting in the loss of pancreatic β-cells and, consequently, in chronic hyperglycemia. Insulin supplementation allows diabetic patients to control their glycaemia quite efficiently, but treated patients still display an overall shortened life expectancy and an altered quality of life as compared to their healthy counterparts. In this context and due to the ever increasing number of diabetics, establishing alternative therapies has become a crucial research goal. Most current efforts therefore aim at generating fully functional insulin-secreting β-like cells using multiple approaches. In this review, we screened the literature published since 2011 and inventoried the selected markers used to characterize insulin-secreting cells generated by in vitro differentiation of stem/precursor cells or by means of in vivo transdifferentiation. By listing these features, we noted important discrepancies when comparing the different approaches for the initial characterization of insulin-producing cells as true β-cells. Considering the recent advances achieved in this field of research, the necessity to establish strict guidelines has become a subject of crucial importance, especially should one contemplate the next step, which is the transplantation of in vitro or ex vivo generated insulin-secreting cells in type 1 diabetic patients.

Proteomic Profiling Reveals the Ambivalent Character of the Mesenchymal Stem Cell Secretome: Assessing the Effect of Preconditioned Media on Isolated Human Islets

“…PDX-1 is a major regulator of numerous genes expressed in β-cells 47 . Its tight control of insulin transcription and translation means that PDX-1 has been used as a specific marker of human mature β-cells 48 , 49 in the majority of β-cell profiling studies performed so far 50 . From this perspective, an altered expression of PDX-1 and insulin could reflect an adaptation to metabolic demands, rather than a change in islet cell phenotype.…”

Review of Advanced Hydrogel-Based Cell Encapsulation Systems for Insulin Delivery in Type 1 Diabetes Mellitus

“…Diabetes mellitus (DM) is currently affecting almost 422 million people worldwide and the global incidence rate is predicted to increase to 552 million by 2030, thereby its increasing prevalence has led to consider such disease as an epidemic of the 21st century [1]. Type 1 diabetes mellitus (T1DM) is seen as an increasing health hazard with an estimated prevalence ranged between 5% and 10% of the total cases of DM worldwide mostly affecting young people [2].…”

FGF-2b and h-PL Transform Duct and Non-Endocrine Human Pancreatic Cells into Endocrine Insulin Secreting Cells by Modulating Differentiating Genes

“…Ducts, acini, and islets can then originate from these less differentiated cells, as already shown in a model of pancreas regeneration [ 40 , 44 , 45 ]. Based on this evidence, cells of ductal origin have been repeatedly used for assaying the ability of a number of molecules, mainly growth factors and hormones, to induce and expand in vitro insulin producing cells [ 46 , 47 , 48 , 49 ].…”