Abstract
Small-caliber tissue-engineered vascular grafts (TEVGs, luminal diameter <6 mm) are promising therapies for coronary or peripheral artery bypassing surgeries or emergency treatments of vascular trauma, and a robust seed cell source is required for scalable manufacturing of small-caliber TEVGs with robust mechanical strength and bioactive endothelium in future. Human-induced pluripotent stem cells (hiPSCs) could serve as a robust cell source to derive functional vascular seed cells and potentially lead to generation of immunocompatible engineered vascular tissues. Up to date, this rising field of small-caliber hiPSC-derived TEVG (hiPSC-TEVG) research has received increasing attention and achieved significant progress. Implantable, small-caliber, hiPSC-TEVGs have been generated. These hiPSC-TEVGs displayed rupture pressure and suture retention strength approaching to those of human native saphenous veins, with vessel wall decellularized and luminal surface endothelialized with monolayer of hiPSC–endothelial cells. Meanwhile, a series of challenges remain in this field, including functional maturity of hiPSC-derived vascular cells, poor elastogenesis, suboptimal efficiency of obtaining hiPSC-derived seed cells, and relative low ready availability of hiPSC-TEVGs, which are waiting to be addressed. This review is conceived to introduce representative achievements and challenges in small-caliber TEVG generation using hiPSCs, and encapsulate the potential solution and future directions.
Impact statement
Generation of small-caliber tissue-engineered vascular grafts (TEVGs) is a promising field, and may significantly benefit clinical treatments of a series of severe cardiovascular diseases or trauma. Application of human-induced pluripotent stem cells (hiPSCs) as seed cell source may further overcome hurdles in the current TEVG generation using primary cells, and lead to efficient manufacturing and application of small-caliber hiPSC-derived TEVGs (hiPSC-TEVGs) in future. This review is dedicated to summarizing representative achievements and scientific hurdles in small-caliber hiPSC-TEVG generation, to provide readers an overall picture of the progress, challenges, and potential future directions of the field.
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