A novel strategy to engineer small-diameter vascular grafts from marrow-derived mesenchymal stem cells

Tissue-engineered blood vessels have mainly relied on endothelial cells (ECs), smooth muscle cells (SMCs), and biocompatible materials. However, long-term results have revealed several material-related failures, such as stenosis, thromboembolization, and the risk of infection. Furthermore, SMCs from elderly persons have reduced capacity in proliferation and collagen production. Mesenchymal stem cells (MSCs) have the ability to differentiate into multiple cell lineages, including osteoblasts, chondrocytes, ECs, and SMCs. In the current experiment, rabbit MSCs were cultured to form a cell sheet. A tissue-engineered vascular graft (TEVG) was fabricated by rolling the MSC sheet around a mandrel. The TEVG was implanted into a defect of the common carotid artery after it was examined macroscopically and microscopically. Hematoxylin and eosin staining showed that cell sheet was composed of five to seven layers of cells with the thickness of 40-50 μm. Results from the adhesion assay revealed that MSCs had similar antiplatelet adhesion property to ECs. Histological analysis of TEVGs showed that the layers of the cell sheet had fully fused in vitro. After implantation, TEVGs had excellent patency and integrated well with the native vessel. The structure of the TEVGs was similar to that of the native artery 4 weeks after implantation. Electron microscopy showed that the implanted TEVGs endothelialized. These results indicated that a completely biological TEVG could be assembled with autologous MSCs. These TEVGs are useful for revascularization in humans, which would reduce the occurrence of complications caused by foreign materials.