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Rolle der endothelialen Stickoxidproduktion bei SDF-1α/TNF-α-vermittelter Migration von Stammzellen in vivo

Role of endothelial nitric oxide synthesis in SDF-1α/TNF-α mediated stem cell migration in vivo

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Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Die regulierenden Signalwege, welche die Migration von therapeutisch applizierten Stammzellen („homing“) beispielsweise in ein ischämisch geschädigtes Myokard vermitteln, sind bisher nur in Ansätzen untersucht. In unserer Arbeitsgruppe haben wir die Interaktionen von Knochenmarkstammzellen und Gefäßendothel, in Abhängigkeit von lokaler Inflammation sowie endothelialer Stickoxid(NO)produktion, in der Mikrozirkulation einer Maus untersucht. Hierzu wurden ein etabliertes Tiermodell sowie die intravitale Fluoreszenzmikroskopie angewandt. Es konnte gezeigt werden, dass die Präsenz des Chemokins SDF-1α in Kombination mit lokaler Stimulation durch TNF-α selektiv die Interaktion von c-kit+-Knochenmarkstammzellen mit dem Gefäßendothel in extramedullärem Gewebe verstärkt. Weiterhin konnte gezeigt werden, dass sowohl die Expression als auch die Funktion der endothelialen NO-Synthase für diesen adhäsionsverstärkenden Effekt von SDF-1α bei einer entzündlichen Gewebssituation unabdingbar sind. Therapieprotokolle, die eine intravaskuläre Stammzellapplikation vorsehen, sollten die lokale endotheliale NO-Produktion als limitierenden Faktor der Zellmigration berücksichtigen.

Abstract

The underlying mechanisms of stem cell migration after therapeutic application to non-marrow tissue, e.g., in ischemia-damaged myocardium, have not been clarified. In order to analyzse the role of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase next toassociated with a local inflammatory response, we studied peripheral c-kit+ stem cell interactions with the local vascular endothelium in vivo using a mouse model of intravital microscopy. We were able to showIn this study, it was shown that besides the presence of SDF-1α, an inflammatory response induced by local tumor necrosis factor-α (TNF-α) treatment is needed for relevant stem cell interactions with the vascular endothelium in vivo. Moreover, the presence of endothelial nitric oxide synthase (eNOS) appears to be a crucial factor for firm c-kit+ stem cell adhesion to the vascular endothelium.

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Danksagung

Die Autoren bedanken sich bei Laboratory Investigation (Nature Publishing Group) für die Zusammenarbeit bei der Zusammenstellung der hier abgedruckten Abbildungen.

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  1. Klinik und Poliklinik für Herzchirurgie, Universität Rostock, Schillingallee 35, 18055, Rostock, Deutschland

    P.J. Donndorf & G. Steinhoff

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  1. P.J. Donndorf
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  2. G. Steinhoff
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Correspondence to P.J. Donndorf.

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Donndorf, P., Steinhoff, G. Rolle der endothelialen Stickoxidproduktion bei SDF-1α/TNF-α-vermittelter Migration von Stammzellen in vivo. Z Herz- Thorax- Gefäßchir 24, 317–323 (2010). https://doi.org/10.1007/s00398-010-0800-3

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  • DOI: https://doi.org/10.1007/s00398-010-0800-3

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