Humane endotheliale Progenitorzellen – Verheißungsvolle Kandidaten für therapeutische Angiogenese?

Zusammenfassung

Die Forschung mit endothelialen Progenitorzellen (EPC) entwickelte sich innerhalb der letzten 15 Jahre besonders dynamisch, EPC wurden zum Hoffnungsträger für die Therapie von kardiovaskulären Erkrankungen. In der Angiogeneseforschung gingen Wissenschaftler von Fragen in der Grundlagenforschung zur Testung zellbasierter Therapien in präklinischen Tiermodellen über. Man isolierte und charakterisierte die biologischen Eigenheiten von putativen EPC aus Blut oder Knochenmark, um ihr therapeutisches Potenzial bereits nach wenigen Jahren in klinischen Studien zu testen. Die klinischen Resultate führten zur Erkenntnis, dass der Effekt von EPC in vivo weniger beeindruckend war als erwartet. Sogenannte EPC entpuppten sich bei strikter Betrachtung von Phänotyp und Funktion als unterschiedliche, zumeist terminal differenzierte hämatopoetische Zellen, die endotheliale Marker koexprimieren. Es hat sich aber erwiesen, dass hämatopoetische Zelltypen eindeutig proangiogene Effekte induzieren können, die man in Zukunft möglicherweise effizient nutzen könnte. Der Artikel bietet einen Überblick über derzeit gültige Definitionen und die Charakterisierung und Isolierung von EPC. Die Grundlagen von Stammzellbiologie und deren Bedeutung für Angiogenese und vaskuläre Homöostase werden diskutiert. Ein Ausblick auf Perspektiven für die therapeutische Angiogenese und auf mögliche Konzepte in der Entwicklung von Zelltherapie als zentrale Säule der regenerativen Medizin wird geboten.

Abstract

The field of endothelial progenitor cells (EPC) has developed with considerable speed into a clinically relevant matter within the last 15 years. EPC generated substantial promise as candidates for a potential reparative cell therapy for a number of human cardiovascular disorders and to improve functional organ recovery. Principles of therapeutic angiogenesis have been discovered in basic studies of isolating and characterizing the biologic properties of EPC and tested in preclinical rodent model systems of cardiovascular diseases. However, clinicians and basic scientists moved rapidly to the delivery of blood- or marrow-derived EPC into selected patients. Clinical EPC effects did not fulfill relatively high expectations. Furthermore, most “EPC” applied in preclinical and clinical studies turned out to be cells of the hematopoietic system which simply coexpressed markers primarily identified on endothelial cells (EC). Meanwhile, a more detailed appreciation has evolved with regard to the roles played by hematopoietic cells in vascular repair. This review will provide an overview on advances in the EPC field to date and focus on the clarification of the EPC definitions and of stem cell biology, angiogenesis and vascular homeostasis that has occurred over the last 5 to 10 years. Eventually, potential novel concepts for therapeutic angiogenesis and perspectives in cell therapy and regenerative medicine will be highlighted.

Schlüsselwörter

endotheliale Progenitorzellen - therapeutische Angiogenese - Zelltherapie

Key words

endothelial progenitor cells (EPC) - therapeutic angiogenesis - cell therapy

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