What's new in stem cells? From cell therapies to personalized genomic medicine for Type 1 Diabetes

Abstract

The treatment of type 1 diabetes (T1D) is entering a transformative period. Complementary therapeutic approaches have made it possible to delay the clinical onset of the disease and achieve increasingly precise, real-time control of blood glucose levels. Key advances include the approval of the first immunomodulatory therapy, teplizumab, and continued progress in automated insulin delivery systems. However, one of the most far-reaching breakthroughs has been the demonstration that transplantation of islets derived from human pluripotent stem cells (SC-islets) can reverse T1D in patients¹. Even more remarkably, preclinical studies have established that SC-islets genetically engineered to lack HLA class I and II molecules while overexpressing CD47—so-called “hypoimmune”—can survive and reverse diabetes without the need for immunosuppression². These advances are bringing cell replacement therapy closer to large-scale clinical implementation and positioning it as a promising path toward a functional cure for T1D. In this talk, I will review the scientific foundations, current challenges, and future prospects of SC-islet-based therapies.

Important challenges remain, including incomplete functional maturation, the presence of unwanted cell populations, and heterogeneity in therapeutic responses among patients³. Our group has contributed to this field by modeling monogenic diabetes through the in vitro differentiation of β-cells from human induced pluripotent stem cells (iPSCs)⁴, showing that genetic defects affecting key transcription factors disrupt the specification and proliferation of pancreatic progenitors, ultimately impairing the generation of functional βcells. These findings, together with a growing body of evidence, highlight the potential influence of a patient’s genetic background on the efficacy of cell-based therapies and underscore the need to better understand the molecular mechanisms underlying β-cell dysfunction in order to optimize cell replacement strategies.

Finally, I will briefly introduce the initiatives we are advancing in Argentina to help translate these developments into national capabilities. We are establishing the Argentine Type 1 Diabetes Genomics Initiative (IG-DT1), which aims to create the first national DNA biobank of individuals with T1D and to develop genetic risk scores (GRSs) for the early identification of at-risk individuals. These tools may enable the stratification of individuals into disease endotypes characterized by a predominant contribution of immune-mediated mechanisms or intrinsic β-cell dysfunction. In parallel, we are promoting the development of local platforms for the differentiation of β-cells from iPSCs. Through close collaboration with the clinical community and the productive sector, our overarching goal is to build national capacity in regenerative medicine and precision genomics for T1D.