Gremlin1-MSCs seeded on small-diameter artificial blood vessels facilitate attenuation of post-transplantation intimal hyperplasia

Artificial blood vessels are commonly used to treat vascular damage and diseases. While large-diameter artificial blood vessels have been widely used in clinical practice, small-diameter artificial blood vessels (<6 mm) face significant challenges, including acute thrombosis in the short-term and intimal hyperplasia in the long-term. In this study, mesenchymal stem cells overexpressing Gremlin1 (Gremlin1-MSCs) were implanted as seed cells on the inner layer of polyurethane (PU) small-diameter artificial blood vessels fabricated by electrospinning technology. Additionally, the adhesion of Gremlin1-MSCs was enhanced by coating the lumen surface of the vessels with polydopamine (PDA). This approach aimed to promote endothelialization, thus reducing the risks of acute thrombosis and intimal hyperplasia. The in vitro results demonstrated that Gremlin1-MSCs retained their MSC characteristics and possessed the ability to inhibit monocyte proliferation and macrophage polarization. Furthermore, the PDA-coated PU small-diameter artificial blood vessels exhibited excellent biocompatibility and hemocompatibility. After implantation in rabbit carotid arteries, Gremlin1-MSCs significantly improved the long-term patency of small-diameter artificial blood vessels and reduced intimal hyperplasia of natural blood vessels at the suture site compared to the control MSCs (Ctrl-MSCs) or no MSCs treatment. This study provides a promising approach to improve the patency of small-diameter artificial blood vessels and highlights the potential of Gremlin1-MSCs as effective seed cells for this application.