Guanylate-binding protein 1 expression from embryonal endothelial progenitor cells reduces blood vessel density and cellular apoptosis in an axially vascularised tissue-engineered construct

BMC Biotechnology

Oliver Bleiziffer¹  Matthias Hammon¹  Andreas Arkudas¹  Christian D Taeger¹  Justus P Beier¹  Kerstin Amann²  Elisabeth Naschberger³  Michael Stürzl³  Raymund E Horch¹  Ulrich Kneser¹ 

[1] Department of Plastic and Hand Surgery, University of Erlangen-Nuremberg, Krankenhausstr 12 91054, Erlangen, Germany

[2] Department of Nephropathology, Erlangen University Medical Center, Krankenhausstr 12 91054, Erlangen, Germany

[3] Division of Molecular and Experimental Surgery, Erlangen University Medical Center, Krankenhausstr 12 91054, Erlangen, Germany

关键词: In vivo tissue engineering;    Guanylate-binding protein 1;    Endothelial progenitor cells;    Angiogenesis;   

Others  :  1131321
DOI  :  10.1186/1472-6750-12-94

 received in 2012-05-20, accepted in 2012-11-07,  发布年份 2012

【 摘 要 】

Background

Guanylate binding protein-1 (GBP-1) is a large GTPase which is actively secreted by endothelial cells. It is a marker and intracellular inhibitor of endothelial cell proliferation, migration, and invasion. We previously demonstrated that stable expression of GBP-1 in murine endothelial progenitor cells (EPC) induces their premature differentiation and decreases their migration capacity in vitro and in vivo. The goal of the present study was to assess the antiangiogenic capacity of EPC expressing GBP-1 (GBP-1-EPC) and their impact on blood vessel formation in an axially vascularized 3-D bioartificial construct in vivo.

Results

Functional in vitro testing demonstrated a significant increase in VEGF secretion by GBP-1-EPC after induction of cell differentiation. Undifferentiated GBP-1-EPC, however, did not secrete increased levels of VEGF compared to undifferentiated control EPC expressing an empty vector (EV-EPC). In our In vivo experiments, we generated axially vascularized tissue-engineered 3-D constructs. The new vascular network arises from an arterio-venous loop (AVL) embedded in a fibrin matrix inside a separation chamber. Total surface area of the construct as calculated from cross sections was larger after transplantation of GBP-1-EPC compared to control EV-EPC. This indicated reduced formation of fibrovascular tissue and less resorption of fibrin matrix compared to constructs containing EV-EPC. Most notably, the ratio of blood vessel surface area over total construct surface area in construct cross sections was significantly reduced in the presence of GBP-1-EPC. This indicates a significant reduction of blood vessel density and thereby inhibition of blood vessel formation from the AVL constructs caused by GBP-1. In addition, GBP-1 expressed from EPC significantly reduced cell apoptosis compared to GBP-1-negative controls.

Conclusion

Transgenic EPC expressing the proinflammatory antiangiogenic GTPase GBP-1 can reduce blood vessel density and inhibit apoptosis in a developing bioartificial vascular network and may become a new powerful tool to manipulate angiogenetic processes in tissue engineering and other pathological conditions such as tumour angiogenesis.

【 授权许可】

   
2012 Bleiziffer et al.; licensee BioMed Central Ltd.

【 图 表 】

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