Title : Stem cell derived beta cells for type 1 diabetes: A review of progress challenges and future directions
Abstract:
Background: Type 1 diabetes mellitus (T1D) is a chronic autoimmune disorder marked by the destruction of pancreatic β-cells, resulting in lifelong insulin dependency and associated complications. Traditional treatments, including insulin therapy, pancreas, and islet transplantation, are limited by donor scarcity, procedural risks, and suboptimal glycaemic control. As such, stem cell-derived β-cell replacement therapy has emerged as a promising strategy to restore endogenous insulin production and offer a potential cure.
Methods: This review synthesises recent literature on the differentiation of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) into functional β-like cells. Key areas explored include: molecular pathways of β-cell maturation, the use of islet-like microenvironments, challenges in achieving functional equivalence to native β-cells, and approaches to prevent immune rejection and tumourigenesis.
Results: Advancements in stepwise differentiation protocols and transcriptional control have yielded β-like cells that increasingly resemble mature human β-cells in phenotype and insulin secretion. Techniques such as islet clustering and metabolic conditioning have improved functional outcomes. However, issues remain, including incomplete maturation (e.g., persistent MAFB expression over MAFA), limited glucose responsiveness, and vulnerability to immune rejection. Strategies such as encapsulation, regulatory T cell (Treg) therapy, and purification methods to reduce tumour risk are under active investigation, though many remain in early experimental stages.
Conclusion: Whilst the field has made significant strides towards generating functional β-cells from stem cells, full clinical translation is hindered by scientific and practical barriers. Further research is required to enhance cellular maturity, ensure long-term graft survival, and safely navigate ethical and immunological challenges. Nonetheless, current progress indicates that stem cell-based β-cell therapy could transform the management of T1D in the foreseeable future.
