TY - JOUR

T1 - Peripheral blood derived endothelial colony forming cells as suitable cell source for pre-endothelialization of arterial vascular grafts under dynamic flow conditions

AU - Kraus, Xenia

AU - van de Flierdt, Edda

AU - Renzelmann, Jannis

AU - Thoms, Stefanie

AU - Witt, Martin

AU - Scheper, Thomas

AU - Blume, Cornelia

N1 - Funding Information: This study was funded by the Deutsche Forschungsgemeinschaft (DFG – Grant Number: 388094931 ). This work has been carried out within the framework of the SMART BIOTECS alliance between the Technische Universitaet Braunschweig and the Leibniz Universität Hannover. This initiative is supported by the Ministry of Economy and Culture (MWK) of Lower Saxony, Germany. We thank C. Nikolin and S. Immenschuh for providing HAEC.

PY - 2022/9

Y1 - 2022/9

N2 - In regenerative medicine, autologous peripheral blood derived endothelial colony forming cells (PB-derived ECFC) represent a promising source of endothelial cells (EC) for pre-endothelialization of arterial tissue engineered vascular grafts (TEVG) since they are readily attainable, can easily be isolated and possess a high proliferation potential. The aim of this study was to compare the phenotype of PB-derived ECFC with arterial and venous model cells such as human aortic endothelial cells (HAEC) and human umbilical vein endothelial cells (HUVEC) under dynamic cell culture conditions to find a suitable cell source of EC for pre-endothelialization. In this study PB-derived ECFC were cultivated over 24 h under a high pulsatile shear stress (20 dyn/cm2, 1 Hz) and subsequently analyzed. ECFC oriented and elongated in the direction of flow and expressed similar anti-thrombotic and endothelial differentiation markers compared to HAEC. There were significant differences observable in gene expression levels of CD31, CD34 and NOTCH4 between ECFC and HUVEC. These results therefore suggest an arterial phenotype for PB-derived ECFC both under static and flow conditions, and this was supported by NOTCH4 protein expression profiles. ECFC also significantly up-regulated gene expression levels of anti-thrombotic genes such as krueppel-like factor 2, endothelial nitric oxide synthase 3 and thrombomodulin under shear stress cultivation as compared to static conditions. Dynamically cultured PB-derived ECFC therefore may be a promising cell source for pre-endothelialization of arterial TEVGs.

AB - In regenerative medicine, autologous peripheral blood derived endothelial colony forming cells (PB-derived ECFC) represent a promising source of endothelial cells (EC) for pre-endothelialization of arterial tissue engineered vascular grafts (TEVG) since they are readily attainable, can easily be isolated and possess a high proliferation potential. The aim of this study was to compare the phenotype of PB-derived ECFC with arterial and venous model cells such as human aortic endothelial cells (HAEC) and human umbilical vein endothelial cells (HUVEC) under dynamic cell culture conditions to find a suitable cell source of EC for pre-endothelialization. In this study PB-derived ECFC were cultivated over 24 h under a high pulsatile shear stress (20 dyn/cm2, 1 Hz) and subsequently analyzed. ECFC oriented and elongated in the direction of flow and expressed similar anti-thrombotic and endothelial differentiation markers compared to HAEC. There were significant differences observable in gene expression levels of CD31, CD34 and NOTCH4 between ECFC and HUVEC. These results therefore suggest an arterial phenotype for PB-derived ECFC both under static and flow conditions, and this was supported by NOTCH4 protein expression profiles. ECFC also significantly up-regulated gene expression levels of anti-thrombotic genes such as krueppel-like factor 2, endothelial nitric oxide synthase 3 and thrombomodulin under shear stress cultivation as compared to static conditions. Dynamically cultured PB-derived ECFC therefore may be a promising cell source for pre-endothelialization of arterial TEVGs.

KW - Arteriovenous differentiation

KW - Endothelial colony forming cells

KW - Endothelialization

KW - Shear stress cultivation

KW - Tissue engineering

KW - Vascular grafts

UR - http://www.scopus.com/inward/record.url?scp=85133493666&partnerID=8YFLogxK

U2 - 10.1016/j.mvr.2022.104402

DO - 10.1016/j.mvr.2022.104402

M3 - Article

C2 - 35753506

AN - SCOPUS:85133493666

VL - 143

JO - Microvascular research

JF - Microvascular research

SN - 0026-2862

M1 - 104402

ER -