Mesenchymal stem cells attenuate diabetic vascular complication by reducing irregular extracellular matrix production in human blood vessel organoids

Abstract

Mesenchymal stem cells (MSCs) hold potential for treating diabetic vascular complications, but current models fail to adequately replicate the complexities of diabetic vascular disease, limiting our ability to accurately assess their therapeutic effects. To this end, we developed a co-culture system using a combination of human embryonic stem cell-derived blood vessel organoids (BVOs) and MSCs. This system could accurately replicate key aspects of diabetic pathology, including basement membrane thickening and excessive extracellular matrix (ECM) deposition. The results showed that MSCs were effective in attenuating basement membrane thickening and reducing ECM deposition in BVOs under diabetic conditions. Subsequent transcriptomics demonstrated that the MSC-treated group exhibited a notable normalization of ECM-related gene expression, particularly in collagen IV levels. Furthermore, the inhibition of the NF-κB signaling pathway was identified as a crucial mechanism underlying the therapeutic efficacy of MSCs. This study demonstrates the potential of MSCs to counteract diabetic vascular complications and emphasizes the co-culture system as a more physiologically relevant model to investigate the preventive and therapeutic potential of MSCs in diabetic pathology.