Abstract
Throughout life, damage to the vascular endothelium is pivotal in the development of cardiovascular disease. Therefore, a detailed understanding of the underlying mechanisms involved in endothelial cell restoration is of fundamental importance for preventive and therapeutic concepts in cardiovascular disease. The goal of regenerative medicine is the use of tissue-specific progenitor cells for a more effective repair process with reduction of fibrocellular remodelling, fibrosis and loss of functional properties.
According to the hitherto assumed primary model of endothelial regeneration only adjacent and intact mature endothelial cells replace damaged endothelium. Since Asahara and colleagues first described that a peripheral blood mononuclear cell population was able to differentiate into endothelial cells in vitro and incorporate into ischemic tissue at sites of angiogenesis in vivo, the model of endothelial regeneration has been extended. The majority of clinical trials on human cell therapy for ischemic vascular disease are based on cell surface antigen expression of CD34 or VEGFR2 to identify endothelial progenitor cells.
A precise characterization of the angiogenic properties of different subsets of endothelial regenerating cells and their course of action to gain sufficient long-term regeneration of the injured vessel is a necessary precondition before clinical trials of human cell therapy become a routine reality.
Zusammenfassung
Die Schädigung von Blutgefäßen, insbesondere der Endothelzellschicht, führt bei fehlender effektiver Gefäßregeneration zur Entstehung atherosklerotischer Läsionen. Dieser durch kardiovaskuläre Risikofaktoren beschleunigte Prozess bedingt degenerative Gefäßwandveränderungen, die mit einem Verlust funktioneller Gefäßeigenschaften einhergehen. Ein gesundes Gefäßendothel bzw. dessen Regeneration und Rekonstruktion nach Schädigung sind daher für die Vermeidung von Atherosklerose und Restenosierungsprozessen nach Koronarintervention von entscheidender Bedeutung. Ziel der regenerativen Medizin ist es, die zellvermittelte Regeneration geschädigter Gefäße als neues Konzept zur Prävention der Atherosklerose zu ermöglichen, insbesondere da eine dauerhafte Reduktion kardiovaskulärer Risikofaktoren im klinischen Alltag schwer zu erreichen ist.
Bislang ging man davon aus, dass die reparativen Mechanismen nach Endothelläsion durch die angrenzenden Endothelzellen via Proliferation und Wachstum per continuitatem erfolgen. Seit der Erstbeschreibung vaskulärer Stammzellen durch Asahara et al., der sog. zirkulierenden endothelialen Vorläuferzellen (EPCs), wurde das traditionelle Modell dahin gehend ergänzt, dass die aus dem Knochenmark stammenden, peripher zirkulierenden Vorläuferzellen als Quelle für den Ersatz untergegangener Endothelzellen fungieren. Die Mehrzahl klinischer Studien bezüglich humaner, zellbasierter Therapien ischämischer Gefäßerkrankungen wurde mit diesen Zellen durchgeführt.
Ein besseres Verständnis der Interaktionen endothelregenerierender somatischer, unreifer Progenitorzellen und tatsächlicher Stammzellen könnte die therapeutischen Ansätze zur endogenen Reparatur maßgeblich verbessern. Insbesondere die Aufklärung der Interaktionen unterschiedlicher zellulärer Subgruppen, die an der Endothelzellregeneration beteiligt sind und die Resolution der akuten Inflammation induzieren, ohne dass eine chronische Entzündung der Gefäßwand entstehen kann, ist daher eine relevante biologische Fragestellung und wichtig für das Verständnis sowie die Verhinderung der Atherosklerose und deren Folgekrankheiten.
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Becher, M., Nickenig, G. & Werner, N. Regeneration of the vascular compartment. Herz 35, 342–351 (2010). https://doi.org/10.1007/s00059-010-3360-0
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DOI: https://doi.org/10.1007/s00059-010-3360-0