Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure
of pancreatic β-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus.
The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional
β-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential
for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into β-
cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative
applications. Progress has also been made in establishing in-vitro culture protocols to yield
definitive endoderm, pancreatic endoderm progenitor cells and β-cells via different reprogramming
strategies and growth factor supplementation. However, these generated β-cells are still immature,
lack functional characteristics and exhibit lower capability in reversing the diseases conditions.
Current methods employed to generate mature and functional β-cells include; use of small and large
molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve
the functional properties and heterogeneity of differentiated cells.
This review details recent advancements in the generation of mature β-cells by reprogramming stem
cells into iPSCs that are further programmed to β-cells. It also provides deeper insight into current reprogramming
protocols and their efficacy, focusing on the underlying mechanism of chemical-based
approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies
both in-vitro and in-vivo to date and the future prospects in the generation of mature β-cells.