Abstract

Adipose stem cells (ASCs) show potential in the recellularization of tissue engineerined vascular grafts (TEVGs). However, whether sphingosine-1-phosphate (S1P) could further enhance the adhesion, proliferation, and antithrombosis of ASCs on decellularized vascular scaffolds is unknown. This study investigated the effect of S1P on the recellularization of TEVGs with ASCs. Human ASCs were derived from lipoaspirate. Scaffolds were derived from human umbilical arteries (HUAs) with treatment of 0.1% sodium dodecyl sulfate (SDS) for 48 h (decellularized HUAs; DHUAs). The adhesion, proliferation, and antithrombotic functions (kinetic clotting time and platelet adhesion) of ASCs on DHUAs with S1P or without S1P were evaluated. The histology and DNA examination revealed a preserved structure and the elimination of the nuclear component more than 95% in HUAs after decellularizaiton. Human ASCs (hASCs) showed CD29(+), CD73(+), CD90(+), CD105(+), CD31(–), CD34(–), CD44(–), HLA-DR(–), and CD146(–) while S1P-treated ASCs showed marker shifting to CD31(+). In contrast to human umbilical vein endothelial cells (HUVECs), S1P didn’t significantly increase proliferation of ASCs on DHUAs. However, the kinetic clotting test revealed prolonged blood clotting in S1P-treated ASC-recellularized DHUAs. S1P also decreased platelet adhesion on ASC-recellularized DHUAs. In addition, S1P treatment increased the syndecan-1 expression of ASCs. TEVG reconstituted with S1P and ASC-recellularized DHUAs showed an antithrombotic effect in vitro. The preliminary results showed that ASCs could adhere to DHUAs and S1P could increase the antithrombotic effect on ASC-recellularized DHUAs. The antithrombotic effect is related to ASCs exhibiting an endothelial-cell-like function and preventing of syndecan-1 shedding. A future animal study is warranted to prove this novel method.

Highlights

  • Adipose stem cells (ASCs) show great potential in regenerative medicine, as they have the ability to differentiate into different lineages

  • Dapi staining confirmed the depletion of nuclear component after Figure 1J: decellularized human umbilical arteries (DHUAs)); DNA quantification showed that more than 95% DNA was removed from the decellularization (Figure 1F: native, Figure 1J: DHUA); DNA quantification showed that more HUtAha(nFi9g5u%reD1NKA, pw

  • Our results indicated that S1P could stimulate a significant increase in the expression of syndecan-1 on ASCs in a way that was similar to human umbilical vein endothelial cells (HUVECs)

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Summary

Introduction

Adipose stem cells (ASCs) show great potential in regenerative medicine, as they have the ability to differentiate into different lineages. ASCs have been considered in the field of tissue engineering technology for tissue or organ fabrication in vitro. The advantages of ASCs in tissue engineering are mainly related to the ease of harvesting a large amount of fat for cell cultivation, the lack of ethical concerns, and their pluripotency [2]. ASCs have been used in tissue engineering research of bone, cartilage, adipose tissue, tendon, skin, and so forth [3,4,5,6]. They have been proposed for use in vascular tissue engineering [7]

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