Type 2 diabetes-induced molecular and functional impairment of adipose tissue-derived mesenchymal stromal cells (ASCs) and interferon gamma priming for enhanced diabetic ASC-based therapy

Study Description: The study identified significant transcriptomic changes associated with T2D in human adipose stromal cells (hASCs) at basal level or after ASC treatment with a mix of proiflammatory cyokines (IFN-γ and TNF-α) for 48 hours. The microarray study comprised four main comparative groups. Group (Gp)1 focused on analyzing the transcriptome profiles of ASCs f from T2D patients (dASCs) with a BMI range from 25-29 kg/m², relative to ndASCs, from healthy donors matched for BMI range. Gp2 included an expanded cohort of T2D patients with a broader BMI range of 25-35 kg/m² (n=8), compared to a corresponding group of healthy donors (n=7). This design enabled focused assessment of transcriptomic variations associated with T2D, excluding the obesity as confounding factor, while also validating findings across a broader and more diverse patient cohort. Moreover, Gp1 and GP2 were reproduced as Gp3 and Gp4, respectively, after priming of ndASCs or dASCs with a mix of of TNF-α and IFN-γ for 48 hours.Integrative computational analysis identified EGFR/ERBB2 signaling and downstream cascades including Ras/MAPK and PI3K/AKT, and endocrine resistance as significantly affected pathways in dASCs.