Tissue Engineered Vascular Grafts Created from Human Induced Pluripotent Stem Cells

The utility of human induced pluripotent stem cells (hiPSCs) to create tissue engineered vascular grafts (TEVGs) was evaluated in this study.  hiPSC lines were first induced into a mesenchymal lineage via a neural crest intermediate using a previously reported serum-free, chemically defined differentiation scheme. Derived cells exhibited commonly known mesenchymal markers (CD90, CD105, CD73; negative markers – CD45), and could differentiate into several mesenchymal lineages (osteogenic, chondrogenic, adipogenic). Functional vascular grafts were then engineered by culturing hiPSC-derived mesenchymal progenitor cells in a pulsatile bioreactor system over 8 weeks, to induce smooth muscle cell differentiation and collagenous matrix generation. Histological analyses confirmed layers of calponin-positive smooth muscle cells in a collagen rich matrix. Mechanical tests revealed that grafts had an average burst pressure of 700 mm Hg, which is approximately half of that of native veins. Overall, these results provide significant insight into the utility of hiPS cells for vascular graft generation. They pave the way for creating personalized, patient-specific vascular grafts for surgical applications, as well as for creating experimental models of vascular development and disease.