Abstract 15383: Rapid in vivo Maturation of Biotube Vascular Grafts by Giant Drops Patching of Adipose-Derived Vascular Stromal Cells Spheroids

Introduction: Adipose-derived stromal cells (ADSCs) is considered to be one of the most promising cell sources for use in cardiovascular tissue regeneration because of their angiogenic potential and easy isolation by liposuction. However, even though ADSCs in suspension were injected into conventional scaffold-based vascular grafts during transplantation, most of them were diffused into surrounding tissues and were hardly engrafted into any vascular grafts. In this study, giant drops of ADSC spheroids were prepared on our specially designed, charged culture dishes for the application to enhancement of in vivo maturation of in-body tissue engineered BIOTUBE autologous vascular grafts. Methods and Results: ADSCs from subcutaneous fat of GFP transgenic rats could self-aggregate only single spheroid in the charged dishes at 24 h after cell seeding with controlling its size from 0.1 mm to over 2 mm in diameter according to the dish size. The ADSC spheroids over 1 mm in diameter could be easily handling by tweezers. On the other hand, BIOTUBEs (diameter: 1.5 mm, length: 10 mm) prepared by placing silicone rods as a mold into dorsal subcutaneous pouches in wild rats for 4 weeks were auto-implanted to abdominal aortas by end-to-end anastomosis with outer surface patching of the three drops of ADSC spheroids having 3.0х105 cells. After 3 weeks of implantation, BIOTUBEs were patent without any aneurysm formation and the drops were not recognized macroscopically. Histological analysis revealed that the GFP expressing cells originated from the implanted ADSCs covered outer surface of BIOTUBEs homogeneously and infiltrated its wall. Surprisingly, the luminal surface of BIOTUBEs were completely covered with endothelial lining, whereas it took more than 3 month to achieve endothelialization in traditional BIOTUBE without patching. Conclusion: Rapid maturation with endothelialization of BIOTUBE grafts was achieved by patching of giant drops of ADSCs spheroids. The combination of these ADSCs-drops with other vascular grafts also may enable us to achieve their rapid vascularization for high patency rate even in long or small caliber grafts as use in coronary arterial bypass grafting.