Type 2 diabetes mellitus limits the glucose-responsive β-like functionality but not pancreatic lineage commitment of induced human adipose-derived stem cells.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, whose prevalence is increasing worldwide. There is a great demand for an effective cure that attains a normal glucose level. The differentiation of mesenchymal stem cells into insulin-producing cells (IPCs) for pancreatic regeneration represents a promising anti-diabetic therapeutic approach. However, the pathogenic milieu of T2DM may affect their differentiation potential. AIM: This study aimed to investigate the impact of the T2DM milieu on the pancreatic differentiation potential of human adipose-derived stem cells (ASCs) in vitro. METHODS: We isolated and cultured ASCs from T2DM (dASCs) and non-diabetic (nASCs) subjects, then we differentiated the cells into IPCs. We evaluated the differentiation potential using dithizone staining, immunofluorescence staining, and gene expression analysis. We examined the functionality of generated cells via glucose challenge assay. RESULTS: Our results revealed that both dASCS and nASCs could be committed to an early endocrine-like phenotype with comparable potential. However, the glucose-stimulated insulin secretion of dASCs-derived IPCs was significantly less than that derived from nASCs. CONCLUSION: T2DM does not affect the pancreatic commitment potential of dASCs. However, ASCs-derived from diabetic patients displayed a reduced capacity to acquire glucose-responsive endocrine characteristics following pancreatic differentiation, exhibiting a limited β-like functionality.