Xenogeneic-free generation of vascular smooth muscle cells from human induced pluripotent stem cells for vascular tissue engineering

• Published in: Acta biomaterialia Vol. 119; pp. 155 - 168
• Main Authors: Luo, Jiesi, Lin, Yuyao, Shi, Xiangyu, Li, Guangxin, Kural, Mehmet H., Anderson, Christopher W., Ellis, Matthew W., Riaz, Muhammad, Tellides, George, Niklason, Laura E., Qyang, Yibing
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2021; Elsevier BV
• Subjects: Animals; Biodegradability; Biodegradation; Blood vessels; Cell Differentiation; Collagen; Differentiation; Human induced pluripotent stem cells; Humans; Immunodeficiency; Induced Pluripotent Stem Cells; Mechanical properties; Mice; Muscle, Smooth, Vascular; Muscles; Myocytes, Smooth Muscle; Pluripotency; Polyglycolic acid; Reagents; Rings (mathematics); Self-assembly; Smooth muscle; Stem cell transplantation; Stem cells; Tissue Engineering; vascular smooth muscle cells; Vascular tissue; vascular tissue engineering; xenogeneic-free; vascular tissue engineering; Human induced pluripotent stem cells; vascular smooth muscle cells; xenogeneic-free
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2020.10.042

Development of mechanically advanced tissue-engineered vascular grafts (TEVGs) from human induced pluripotent stem cell (hiPSC)-derived vascular smooth muscle cells (hiPSC-VSMCs) offers an innovative approach to replace or bypass diseased blood vessels. To move current hiPSC-TEVGs toward clinical application, it is essential to obtain hiPSC-VSMC-derived tissues under xenogeneic-free conditions, meaning without the use of any animal-derived reagents. Many approaches in VSMC differentiation of hiPSCs have been reported, although a xenogeneic-free method for generating hiPSC-VSMCs suitable for vascular tissue engineering has yet to be established. Based on our previously established standard method of xenogeneic VSMC differentiation, we have replaced all animal-derived reagents with functional counterparts of human origin and successfully derived functional xenogeneic-free hiPSC-VSMCs (XF-hiPSC-VSMCs). Next, our group developed tissue rings via cellular self-assembly from XF-hiPSC-VSMCs, which exhibited comparable mechanical strength to those developed from xenogeneic hiPSC-VSMCs. Moreover, by seeding XF-hiPSC-VSMCs onto biodegradable polyglycolic acid (PGA) scaffolds, we generated engineered vascular tissues presenting effective collagen deposition which were suitable for implantation into an immunodeficient mice model. In conclusion, our xenogeneic-free conditions for generating hiPSC-VSMCs produce cells with the comparable capacity for vascular tissue engineering as standard xenogeneic protocols, thereby moving the hiPSC-TEVG technology one step closer to safe and efficacious clinical translation. [Display omitted]