Tissue-Engineered Vascular Grafts Created From Human Induced Pluripotent Stem Cells

Abstract

The utility of human induced pluripotent stem cells (hiPSCs) to create tissue-engineered vascular grafts was evaluated in this study. hiPSC lines were first induced into a mesenchymal lineage via a neural crest intermediate using a serum-free, chemically defined differentiation scheme. Derived cells exhibited commonly known mesenchymal markers (CD90, CD105, and CD73 and negative marker CD45) and were shown to differentiate into several mesenchymal lineages (osteogenic, chondrogenic, and 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 mmHg, which is approximately half that of native veins. Additionally, studies revealed that karyotypically normal mesenchymal stem cell clones led to generation of grafts with predicted features of engineered vascular grafts, whereas derived clones having chromosomal abnormalities generated calcified vessel constructs, possibly because of cell apoptosis during culture. 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.

Implantable tissue-engineered blood vessels from human induced pluripotent stem cells

“…hiPSCs can self-renew and differentiate into virtually every cell type in the body, including functional VSMCs (hiPSC-VSMCs) [8, 9]. Mesenchymal precursor cells derived from hiPSCs have previously been used to co-culture with endothelial cells in a collagen-fibronectin gel to form microvessels [10] or to create TEBVs with biodegradable polymer scaffolds [11]. However, the suture strength of TEBV based on these hiPSC-derived mesenchymal progenitors was relatively weak (30 g) and unsuitable for arterial implantation [11].…”

Mechanical properties of endothelialized fibroblast-derived vascular scaffolds stimulated in a bioreactor

“…This limited access to ade-55 quate replacement vessels is especially problematic for patients 56 requiring repeated bypass procedures [2]. Synthetic prostheses, 57 while very appropriate for large-diameter applications (>6 mm), 58 have intrinsic inadequate patency rates when used as CABG or 59 for peripheral vascular repair below the knee related to their pro- In order to produce TEBV using 3D scaffolds, many groups have 84 investigated the combination of allogeneic vascular matrices 85 derived from human cadaveric or animal tissue and vascular or 86 mesenchymal cells, or induced pluripotent stem cells [9,15,16]. 87 Another strategy without the use of cells involved heparin-coated 88 decellularized porcine aortas [17].…”

Stem cells for tissue engineered vascular bypass grafts

“…In one of pioneering approaches utilizing hiPS cell lines, the pluripotent cells were first induced into a mesenchymal lineage using a neural crest intermediate stage (Sundaram et al 2014). The derived mesenchymal progenitor cells, which displayed properties similar to marrow stromal cells, were then cultured in a pulsatile bioreactor system over 8 weeks.…”