Mechanical influences on endothelial cell network formation in vitro

A. Groothuis; C. J. Wilson; G. Kasper; K. M. van Scherpenzeel; P. Simon; H. J. Bail; M. A. Schütz; G. N. Duda

doi:10.1055/s-0037-1619945

Osteologie, Inhaltsverzeichnis

Osteologie 2010; 19(03): 250-254
DOI: 10.1055/s-0037-1619945

Bone mechanobiology

Schattauer GmbH

Mechanical influences on endothelial cell network formation in vitro

Mechanische Einflüsse auf die Netzwerkbildung von Endothelzellen in vitro

A. Groothuis^*

¹Julius Wolff Institut, Charité – Universitätsmedizin Berlin, Deutschland

²Centrum für Muskuloskeletale Chirurgie, Charité - Universitätsmedizin Berlin, Deutschland

,

C. J. Wilson^*

¹Julius Wolff Institut, Charité – Universitätsmedizin Berlin, Deutschland

²Centrum für Muskuloskeletale Chirurgie, Charité - Universitätsmedizin Berlin, Deutschland

,

G. Kasper

¹Julius Wolff Institut, Charité – Universitätsmedizin Berlin, Deutschland

²Centrum für Muskuloskeletale Chirurgie, Charité - Universitätsmedizin Berlin, Deutschland

³Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Deutschland

⁺current affiliation: Clinical Research, Friadent GmbH, Mannheim, Deutschland

,

K. M. van Scherpenzeel

²Centrum für Muskuloskeletale Chirurgie, Charité - Universitätsmedizin Berlin, Deutschland

,

P. Simon

²Centrum für Muskuloskeletale Chirurgie, Charité - Universitätsmedizin Berlin, Deutschland

,

H. J. Bail

⁴Klinik für Unfall- und Orthopädische Chirurgie, Klinikum Nürnberg Süd, Nürnberg, Deutschland

,

M. A. Schütz

⁵Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australien

⁶Trauma Service/Orthopaedics, Princess Alexandra Hospital, Brisbane, Australien

,

G. N. Duda

¹Julius Wolff Institut, Charité – Universitätsmedizin Berlin, Deutschland

²Centrum für Muskuloskeletale Chirurgie, Charité - Universitätsmedizin Berlin, Deutschland

³Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Deutschland

› Institutsangaben

Abstract

Summary

While both the restoration of the blood supply and an appropriate local mechanical environment are critical for uneventful bone healing, their influence on each other remains unclear. Human bone fracture haematomas (< 72 h post-trauma) were cultivated for 3 days in fibrin matrices, with or without cyclic compression. Conditioned medium from these cultures enhanced the formation of vessel-like networks by HMEC-1 cells, and mechanical loading further elevated it, without affecting the cells’ metabolic activity. While haematomas released the angiogenesis-regulators, VEGF and TGF-β1, their concentrations were not affected by mechanical loading. However, direct cyclic stretching of the HMEC-1 cells decreased network formation. The appearance of the networks and a trend towards elevated VEGF under strain suggested physical disruption rather than biochemical modulation as the responsible mechanism. Thus, early fracture haematomas and their mechanical loading increase the paracrine stimulation of endothelial organisation in vitro, but direct periodic strains may disrupt or impair vessel assembly in otherwise favourable conditions.

Zusammenfassung

Eine komplikationslose Knochenheilung ist sowohl von der Wiederherstellung der Blutversorgung als auch einer geeigneten mechanischen Umgebung abhängig. Die gegenseitige Wechselwirkung beider Parameter ist bisher weitgehend unbekannt. Humane Frakturhämatome (< 72 h nach dem Trauma) wurden für drei Tage in einer Fibrin-Matrix mit/ohne zyklische/r Kompression kultiviert. Das konditionierte Medium dieser Kulturen stimulierte parakrin die Bildung gefäßähnlicher Netzwerke durch HMEC-1-Zellen. Dieser Effekt konnte durch mechanische Stimulation verstärkt werden, ohne die metabolische Aktivität der Zellen zu beeinträchtigen. Die Hämatome sezernierten angiogeneseregulierende Wachstumsfaktoren, VEGF und TGF-β1, deren Konzentration jedoch nicht mechanisch reguliert wurde. Direkte zyklische Dehnung von HMEC-1-Zellen reduzierte jedoch die Netzwerkbildung. Die Morphologie der Netzwerke und die Tendenz zu erhöhter VEGF-Sekretion nach mechanischer Belastung sprechen eher für eine physische als eine biochemische Modulation als möglichen Grund für die reduzierte Netzwerkbildung.

Keywords

Angiogenesis - mechanical stimulation - haematoma

Schlüsselwörter

Angiogenese - mechanische Stimulation - Hämatom

Volltext

Referenzen

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