Human Induced Pluripotent Stem Cell-Derived Vascular Cells: Recent Progress and Future Directions

• Type of Material: Article
• Authors: Jee Eun Oh, Yonsei University; Cholomi Jung, Yonsei University; Young Yoon, Emory University
• Language: English
• Date: 2021-11-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/jcdd8110148
• Title of Journal or Parent Work: JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
• Volume: 8
• Issue: 11
• Grant/Funding Information: This research was supported by grants from NHLBI (R01HL150877, R61 HL154116), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (HI16C2211), and National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (No. 2020R1A2C3003784, No.2020M3A9I4038454).
• Keywords: regenerative medicine; THERAPEUTIC ANGIOGENESIS; Science & Technology; MYOCARDIAL-INFARCTION; HIGHLY EFFICIENT; MESENCHYMAL STEM; SMOOTH-MUSCLE-CELLS; human induced pluripotent stem cell; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; FIBROBLAST-GROWTH-FACTOR; smooth muscle cell; endothelial cell; Cardiovascular System & Cardiology; FUNCTIONAL ENDOTHELIAL-CELLS; NITRIC-OXIDE; stem cell; SIGNALING PROMOTES NEURALIZATION; cardiovascular disease; SERUM RESPONSE FACTOR
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Human induced pluripotent stem cells (hiPSCs) hold great promise for cardiovascular regeneration following ischemic injury. Considerable effort has been made toward the development and optimization of methods to differentiate hiPSCs into vascular cells, such as endothelial and smooth muscle cells (ECs and SMCs). In particular, hiPSC-derived ECs have shown robust potential for promoting neovascularization in animal models of cardiovascular diseases, potentially achieving significant and sustained therapeutic benefits. However, the use of hiPSC-derived SMCs that possess high therapeutic relevance is a relatively new area of investigation, still in the earlier investigational stages. In this review, we first discuss different methodologies to derive vascular cells from hiPSCs with a particular emphasis on the role of key developmental signals. Furthermore, we propose a standardized framework for assessing and defining the EC and SMC identity that might be suitable for inducing tissue repair and regeneration. We then highlight the regenerative effects of hiPSC-derived vascular cells on animal models of myocardial infarction and hindlimb ischemia. Finally, we address several obstacles that need to be overcome to fully implement the use of hiPSC-derived vascular cells for clinical application.