Tissue-Engineered Vascular Grafts with Advanced Mechanical Strength from Human iPSCs

• Published in: Cell stem cell 2020-02, Vol.26 (2), p.251-261.e8
• Main Authors: Luo, Jiesi, Qin, Lingfeng, Zhao, Liping, Gui, Liqiong, Ellis, Matthew W., Huang, Yan, Kural, Mehmet H., Clark, J. Alexander, Ono, Shun, Wang, Juan, Yuan, Yifan, Zhang, Shang-Min, Cong, Xiaoqiang, Li, Guangxin, Riaz, Muhammad, Lopez, Colleen, Hotta, Akitsu, Campbell, Stuart, Tellides, George, Dardik, Alan, Niklason, Laura E., Qyang, Yibing
• Format: Article
• Language: English
• Subjects: Blood Vessel Prosthesis; human induced pluripotent stem cells; Humans; Induced Pluripotent Stem Cells; Myocytes, Smooth Muscle; tissue engineered vascular grafts; Tissue Engineering; vascular smooth muscle cells
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2019.12.012

Vascular smooth muscle cells (VSMCs) can be derived in large numbers from human induced pluripotent stem cells (hiPSCs) for producing tissue-engineered vascular grafts (TEVGs). However, hiPSC-derived TEVGs are hampered by low mechanical strength and significant radial dilation after implantation. Here, we report generation of hiPSC-derived TEVGs with mechanical strength comparable to native vessels used in arterial bypass grafts by utilizing biodegradable scaffolds, incremental pulsatile stretching, and optimal culture conditions. Following implantation into a rat aortic model, hiPSC-derived TEVGs show excellent patency without luminal dilation and effectively maintain mechanical and contractile function. This study provides a foundation for future production of non-immunogenic, cellularized hiPSC-derived TEVGs composed of allogenic vascular cells, potentially serving needs to a considerable number of patients whose dysfunctional vascular cells preclude TEVG generation via other methods. [Display omitted] •Functional VSMCs could be efficiently generated on a large scale from hiPSCs•Optimized biochemical and biophysical conditions were used to generate hiPSC-TEVGs•hiPSC-TEVGs presented mechanical strength comparable to that of saphenous veins•hiPSC-TEVGs maintained patency and mechanical function following rat implantation Luo et al. generated tissue-engineered vascular grafts (TEVGs) using human induced pluripotent stem cell (hiPSC)-derived vascular smooth muscle cells. These hiPSC-derived TEVGs displayed mechanical strength comparable to that of native vessels used clinically as vascular grafts and maintained excellent patency and mechanical function following implantation into a rat model.