Engineering Functional Vascular Media From Hair Follicle Derived Mesenchymal Stem Cells and Small Intestinal Submucosa

In previous studies, we showed that hair follicle stem cells can differentiate to mesenchymal lineages such as adipocytes, chondrocytes, osteoblasts and smooth muscle cells. We successfully isolated smooth muscle cells from hair follicle stem cells (HF-SMC) using a tissue-specific promoter and flow cytometry sorting. HF-SMC expressed several markers of vascular smooth muscle cells, exhibited vascular contractility and demonstrated high proliferation and clonogenic potential, suggesting they might be a good alternative cell source for vascular engineering. Here we aimed at engineering an arterial substitute using HF-SMC and a strong, natural biomaterial namely small intestine submucosa (SIS). Under proper mechanical strain, HF-SMC aligned and exhibited vascular reactivity through receptor and non-receptor mediated pathways as early as 24 hr after cell seeding. After two weeks in culture, the HF-SMC proliferated, migrated into SIS and secreted collagen and elastin, the two major extracellular matrix components of the vessel wall. Notably, vascular reactivity increased significantly and for some agonists approached that of native arteries. The constructs also exhibited similar elasticity and strength as native artery. For the implantation we made tubular constructs that were seeded with endothelial cells, which aligned under application of pulsatile flow. Interestingly, ex-vivo artery bypass experiments showed that confluent endothelial monolayers demonstrated anti-platelet adhesion and anticoagulant properties. Taken together our data suggests that SIS-based vascular constructs may have the potential for arterial implantation.