Targeting β-cell dedifferentiation and transdifferentiation: opportunities and challenges

• Main Authors: Wenrui Wang, Chuan Zhang
• Format: Article
• Language: English
• Published: Bioscientifica 2021-08-01
• Series: Endocrine Connections
• Subjects: dedifferentiation; transdifferentiation; β-cell; diabetes
• Online Access: https://ec.bioscientifica.com/view/journals/ec/10/8/EC-21-0260.xml

The most distinctive pathological characteristics of diabetes mellitus induced by various stressors or immune-mediated injuries are reductions of pancreatic islet β-cell populations and activity. Existing treatment strategies cannot slow disease progression; consequently, research to genetically engineer β-cell mimetics through bi-directional plasticity is ongoing. The current consensus implicates β-cell dedifferentiation as the primary etiology of reduced β-cell mass and activity. This review aims to summarize the etiology and proposed mechanisms of β-cell dedifferentiation and to explore the possibility that ther e might be a time interval from the onset of β-cell dysfunction caused by dedifferentiation to the development of diabetes, which may offer a therapeutic wi ndow to reduce β-cell injury and to stabilize functionality. In addition, to investigate β-cell plasticity, we review strategies for β-cell regeneration utilizing genetic programming, small molecules, cytokines, and bioengineering to transdifferentiate other cell types into β-cells; the development of biomimetic acellular constructs to generate fully functional β-cell-mimetics. However, the maturation of regenerated β-cells is currently limited. Further studies are needed to develop simple and efficient reprogramming methods for assembling perfectly functional β-cells. Future investigations are necessary to transform diabetes into a potentially curable disease.