Endothelial cells derived from iPSC in response to diabetic medium

Diabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. We report the development of 3D blood vessel organoids from human embryonic and induced pluripotent stem cells. These human blood vessel organoids contain endothelium, perivascular pericytes, and basal membranes, and self-assemble into lumenized interconnected capillary networks. We treat these vascular organoids with hyperglycemia and inflammatory cytokines in vitro, which leads to basement membrane thickening, a structural hallmark of diabetic patient. To compare differential gene expression we performed RNAseq on endothelial cells, derived from control (NG) or diabetic (DI) vascular organoids. Overall design: Vascular organoids were differentiated from human iPS cells and treated for 3 weeks with a diabetic media containing 75mM Glucose, 1ng/mL TNF-a, 1ng/mL IL6 (DI) or left untreated in 17mM Glucose (NG). Endothelial cells were FACS sorted for CD31 directly into Trizol and stored at -80°C before RNA preparation. The 2 NG and 2 DI are pools of sorted endothelial cells from multiple vascular organoids (>100) from 2 independent differentiations/treatments.

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Wimmer RA, Leopoldi A, Aichinger M, Wick N, Hantusch B, Novatchkova M, Taubenschmid J, Hämmerle M, Esk C, Bagley JA, Lindenhofer D, Chen G, Boehm M, Agu CA, Yang F, Fu B, Zuber J, Knoblich JA, Kerjaschki D, Penninger JM