Sphingosine-1-phosphate in Endothelial Cell Recellularization Improves Patency and Endothelialization of Decellularized Vascular Grafts In Vivo

Abstract

Background: S1P has been shown to improve the endothelialization of decellularized vascular grafts in vitro. Here, we evaluated the potential of tissue-engineered vascular grafts (TEVGs) constructed by ECs and S1P on decellularized vascular scaffolds in a rat model. Methods: Rat aorta was decellularized mainly by 0.1% SDS and characterized by histology. Rat ECs, were seeded onto decellularized scaffolds, and the viability of the ECs was evaluated by biochemical assays. Then, we investigated the in vivo patency rate and endothelialization for five groups of decellularized vascular grafts (each n = 6) in a rat abdominal aorta model for 14 days. The five groups included (1) rat allogenic aorta (RAA); (2) decellularized RAA (DRAA); (3) DRAA with S1P (DRAA/S1P); (4) DRAA with EC recellularization (DRAA/EC); and (5) DRAA with S1P and EC recellularization (DRAA/EC/S1P). Results: In vitro, ECs were identified by the uptake of Dil-Ac-LDL. S1P enhanced the expression of syndecan-1 on ECs and supported the proliferation of ECs on decellularized vascular grafts. In vivo, RAA and DRAA/EC/S1P both had 100% patency without thrombus formation within 14 days. Better endothelialization, more wall structure maintenance and less inflammation were noted in the DRAA/EC/S1P group. In contrast, there was thrombus formation in the DRAA, DRAA/S1P and DRAA/EC groups. Conclusion: S1P could inhibit thrombus formation to improve the patency rate of EC-covered decellularized vascular grafts in vivo and may play an important role in the construction of TEVGs.

Vascular Tissue Engineering: Polymers and Methodologies for Small Caliber Vascular Grafts

“…Various vessels have been decellularized in order to obtain a vascular graft, as for example, the carotid artery ( 30 ), aorta artery ( 32 , 60 ), internal mammary artery ( 61 ), umbilical artery ( 62 ), saphenous vein ( 63 ), coronary artery ( 64 ), femoral vein ( 58 ), and the vena cava ( 55 ). The protocols for vessel decellularization include a number of agents, such as surfactants, enzymes, solvents, and physical methods.…”

“…Some studies also combine physical methods for chemical or biological agents in order to increase the penetration of agents and increase the decellularization of vascular tissue ( 32 , 55 , 60 , 61 ). Simsa and colleagues evaluated the decellularization of vena cavas with TritonX-100, TnBP, and DNase under static, agitation, and perfusion conditions.…”

“…In order to increase the success of scaffolds, some research has modified the surface of decellularized vessels. Biomolecules that improve endothelization or that prevent hyperplasia and thrombogenesis have been added to decellularized scaffolds ( 29 , 60 , 67 ). In their study, Dimitrievska and colleagues immobilized the anticoagulant heparin on decellularized aorta arteries and evaluated the adhesion of platelets to their surface.…”

Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft

“…After the 14-day follow-up, only one of six rats was alive in the non-endothelialization group, the vascular grafts were short of ECs and there was endothelial damage and thrombotic plaque formation on the luminal side. In contrast, four of six rats were alive in the re-endothelialization groups, ECs are observed in the implanted vascular grafts and there were fewer thrombotic plaques or fibrin clots that were noted in the lumen [ 83 ]. Besides, compared with the control group, the decellularized vessels of re-endothelialization in vitro retained >95% monolayer EC coverage in 1 h after implantation, endothelial coverage increased.…”

The Antithrombotic Function of Sphingosine-1-Phosphate on Human Adipose-Stem-Cell-Recellularized Tissue Engineered Vascular Graft In Vitro

“…In our previous work, we found that using S1P to enhance EC attachment in a tissue-engineered vascular scaffold and the S1P-augmented endothelium significantly enhanced antithrombotic surface properties due to reduced syndecan-1 (SDC-1) shedding [25]. Furthermore, we demonstrated that S1P enhances the patency of EC-recellularized vascular scaffolds in a rat aorta implantation model [26]. The main point of S1P on EC that could prevent platelet adhesion because it promotes SDC-1 expression and prevents SDC-1 shedding.…”