Abstract: PO2128
Modeling Endothelial Cell Dysfunction Using Human Induced Pluripotent Stem Cells Derived from Patients with ESRD
Session Information
- Mechanisms of Kidney and Vascular Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Hong, Suyeon, Uijeongbu St. Mary’s Hospital, Uijeongbu, Korea (the Republic of)
- Lim, Sun Woo, Transplant research center, Seoul, Korea (the Republic of)
- Shin, Yoo-Jin, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
- Ko, Eun jeong, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
- Chung, Byung ha, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
- Yang, Chul Woo, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
Background
Endothelial cell (EC) dysfunction is a frequent feature in end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cell-derived EC (hiPSC-ECs) from patients with ESRD as a model to investigate EC dysfunction.
Methods
hiPSCs were obtained using peripheral blood mononuclear cells of patients with ESRD and healthy controls (HC). Next, we generated hiPSC-ECs and the expression of endothelial markers was assessed by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray were compared between the ESRD and HC groups.
Results
In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on iPSC or EC marker expression. However, the efficiency of EC generation from hiPSC was lower in ESRD than HCs. In addition, ESRD-hiPSC-ECs failed to form interconnecting branching point networks, unlike HC-hiPSC-ECs in the tube formation assays. In a microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs compared with HC-hiPSC-ECs.
Conclusion
In conclusion, ESRD-hiPSC-ECs showed a greater EC dysfunction based on functional assays and molecular profiles and it can be a useful disease model to investigate EC dysfunction in ESRD.
Funding
- Government Support - Non-U.S.