Reprogramming of Different Cell Lineages into Functional β-Cell Substitutes

Since its first use in 1922, insulin therapy has transformed diabetes from a fatal disease to a manageable condition. However, long-term insulin injections lead to significant complications. β-cell replacement, derived from either a limited number of deceased donors or embryonic stem cells, offers an encouraging alternative. While these procedures allow patients to be insulin-independent, they still require systemic immunosuppressants to prevent graft rejection, which poses immunological challenges. Direct reprogramming holds considerable promise as a method for generating β-cells from various sources, enabling autologous therapies that mitigate the risk of immune rejection and eliminate the need to harvest cells from embryos. This review provides an overview of the latest advances in direct reprogramming strategies, with a focus on key transcriptional regulators that drive phenotypic conversion and maintenance of various cell types into β-like cells.