Exploring the effects of Nano-liposomal TGF-β1 on induced pluripotent stem Cell-Derived vascular smooth muscle cells in Tissue-Engineered vascular graft; an in vivo study

다국어 초록 (Multilingual Abstract)

This study explores the impact of liposomal Transforming Growth Factor β1 (TGF-β1) on phenotypic switching inVascular Smooth Muscle Cells (VSMCs) derived from induced pluripotent stem cells (iPSCs) for arterial tissueengineering. We present an innovative approach to reducing graft waiting periods effectively. Using a biomimeticperfusion system, biological scaffolds were developed from sheep’s carotid artery to create Tissue-Engineered Vessels (TEVs). VSMCs derived from rabbit iPSCs were reseeded onto these TEVs to promote proliferation.
TGF-β1 was encapsulated in liposomes using the thin-film hydration method to enhance VSMC growth.
The controlled release of TGF-β1 from these liposomes was quantified through enzyme-linked immunosorbentassay (ELISA). Nano-liposomal TGF-β1 was loaded into the scaffolds at a concentration of 50 ng/mL, with therelease monitored through ELISA. The proliferative activity of VSMCs was evaluated using the CCK8 kit.
Techniques such as real-time PCR, Western blot, Immunohistochemistry, and Flowcytometry were employed toassess VSMC phenotypic switching. Liposomal TGF-β1 treatment led to a 122.30 % increase in cell proliferationrate in TEVs compared to the control group, indicating no cytotoxicity. ELISA results confirmed a controlled andsustained release of liposomal TGF-β1. Furthermore, we demonstrated the efficacy of liposomal TGF-β1 forsustained delivery over an extended period by implanting the grafts in rabbit aortas and monitoring their performancefor four weeks. Our findings highlight the role of Nano-liposomal TGF-β1 in inducing phenotypictransformation within TEVs. This research underscores the promising therapeutic potential of Nano-liposomalTGF-β1 in advancing blood vessel tissue engineering, offering novel pathways for clinical application andaddressing the critical need for improved vascular graft outcomes. In conclusion, our study showcases thesynergy between a biomimetic environment and Nano-liposomal TGF-β1 on rabbit induced pluripotent stem cellderivedVSMCs, emphasizing the significant increase in SMC proliferation, controlled release of TGF-β1, successfulgraft implantation, and the pioneering approach in arterial tissue engineering through the development ofTEVs from sheep carotid arteries.