Comparative Study of Human Pluripotent Stem Cell-Derived Endothelial Cells in Hydrogel-Based Culture Systems

Authors

Zhanqi Wang, Beijing Anzhen Hospital of Capital Medical University, Beijing, China
Fuxing Zuo, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Qing Liu, Beijing Obstetrics and Gynecology Hospital Capital Medical University, Beijing, China
Xuesheng Wu, School of Pharmaceutical Sciences, Peking University, Beijing, China
Qian Du, University of Nebraska - LincolnFollow
Yuguo Lei, University of Nebraska - LincolnFollow
Zhangmin Wu, Beijing Anzhen Hospital of Capital Medical University, Beijing, China
Haishuang Lin, School of Pharmaceutical Sciences, Peking University, Beijing, China

Document Type

Article

Date of this Version

3-2-2021

Citation

CC BY

Abstract

Human pluripotent stem cell (hPSC)-derived endothelial cells (ECs) are promising cell sources for drug discovery, tissue engineering, and studying or treating vascular diseases. However, hPSC-ECs derived from different culture methods display different phenotypes. Herein, we made a detailed comparative study of hPSC-ECs from three different culture systems (e.g., 2D, 3D PNIPAAm-PEG hydrogel, and 3D alginate hydrogel cultures) based on our previous reports. We expanded hPSCs and differentiated them into ECs in three culture systems. Both 3D hydrogel systems could mimic an in vivo physiologically relevant microenvironment to protect cells from shear force and prevent cell agglomeration, leading to a high culture efficiency and a high volumetric yield. We demonstrated that hPSC-ECs produced from both hydrogel systems had similar results as 2D-ECs. The transcriptome analysis showed that PEG-ECs and alginate-ECs displayed a functional phenotype due to their higher gene expressions in vasculature development, extracellular matrix, angiogenesis, and glycolysis, while 2D-ECs showed a proliferative phenotype due to their higher gene expressions in cell proliferation. Taken together, both PEG- and alginate-hydrogel systems will significantly advance the applications of hPSC-ECs in various biomedical fields.