Abstract
Endogenous pancreatic β cell regeneration is a potential strategy for β cell expansion or neogenesis to treat diabetes. Regeneration can occur through stimulation of existing β cell replication or conversion of other pancreatic cells into β cells. Recently, various strategies and approaches for stimulation of endogenous β cell regeneration have been evaluated, but they were not suitable for clinical application. In this paper, we comprehensively review these strategies, and further discuss various factors involved in regulation of β cell regeneration under physiological or pathological conditions, such as mediators, transcription factors, signaling pathways, and potential pharmaceutical drugs. Furthermore, we discuss possible reasons for the failure of regenerative medicines in clinical trials, and possible strategies for improving β cell regeneration. As β cell heterogeneity and plasticity determines their function and environmental adaptability, we focus on β cell subtype markers and discuss the importance of research evaluating the characteristics of new β cells. In addition, based on the autoimmunologic features of type 1 diabetes, NOD/Lt-SCID-IL2rgnull (NSG) mice grafted with human immune cells and β cells are recommended for use in evaluation of antidiabetic regenerative medicines. This review will further understand current advances in endogenous β cell regeneration, and provide potential new strategies for the treatment of diabetes focused on cell therapy.
Highlights
The pancreas plays an essential role in energy consumption and metabolism
Lineage tracing studies in mice have demonstrated that Pdx1-positive multipotent pancreatic progenitor cells (MPCs) possess high proliferative ability and can differentiate into all cell types in each of the three major pancreatic compartments [73, 74]
Numerous studies have documented that ectopic expression of human DTR driven by insulin or glucagon promoters resulted in targeted ablation of 99% of α or β cells following diphtheria toxin (DT) administration [94, 95, 146]
Summary
The pancreas plays an essential role in energy consumption and metabolism. It consists of two functionally and morphologically distinct components: the exocrine and endocrine. Lineage tracing studies in mice have demonstrated that Pdx1-positive MPCs possess high proliferative ability and can differentiate into all cell types in each of the three major pancreatic compartments (exocrine, endocrine, and ductal) [73, 74]. In the PDL mouse model, pancreatic duct cells positive for the expression of carbonic anhydrase II, a duct cell-specific marker, act as progenitors of new islets and exocrine cells after injury [88,89,90].
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