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Herstellung kardiovaskulären Gewebes aus dezellularisiertem biologischem Material

Cardiovascular tissue engineered from decellularized biological material

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

Zusammenfassung

Ziel der Arbeit

Die vorliegende Synopsis bietet einen Überblick über Untersuchungen der Autoren zur Herstellung funktionaler kardiovaskulärer Gewebe aus dezellularisiertem biologischem Material.

Material und Methoden

Eigene Untersuchungen zur Herstellung funktionaler kardiovaskulärer Gewebe werden präsentiert: 1) Ergebnisse nach Ross-Operation mit Verwendung tissue-engineerter Pulmonalklappen, 2) Entwicklung eines Modells zur Dezellularisierung von Schweineherzen, 3) Anwendung dieses Modells auf Aorten‑, Pulmonal‑, Mitral- und Trikuspidalklappen, 4) Rebesiedlung aller Klappen mit Endothelzellen der humanen Nabelschnur in einem selbst konstruierten Bioreaktor, 5) Anwendung desselben Modells zur Dezellularisierung von Aortenbogen sowie Untersuchung ihrer mechanischen Eigenschaften und Unterschiede zu herkömmlichen Dacrongrafts in vivo.

Ergebnisse

Tissue-engineerte Pulmonalklappen erzielten positive klinische Ergebnisse. Dezellularisierungsmodell und Bioreaktor zeigten eine nahezu komplette Dezellularisierung der Herzklappen mit darauffolgender fehlerfreier Rebesiedlung. Tissue-engineerte und native Aortengrafts weisen sehr ähnliche mechanische Eigenschaften auf, im Gegensatz zu Dacrongrafts.

Schlussfolgerung

Die Ergebnisse deuten auf ein großes Potenzial des Tissue-Engineering bei kardiovaskulären Erkrankungen hin. Vor allem die positiven klinischen Erfahrungen bei der Therapie von Klappenvitien, hier gezeigt am Beispiel der Pulmonalklappe, untermauern die zukünftige Bedeutung dieses Therapieansatzes. Fortwährende In-vivo-Studien sind notwendig, um die hier vorgestellten Kurzzeitergebnisse auf längerfristige Anwendbarkeit und somit auf ihren klinischen Stellenwert für die spätere humane Anwendung effektiv zu prüfen.

Abstract

Objectives

This work provides a detailed overview of investigations aimed at generating functional cardiovascular tissue from decellularized biological substances.

Material and methods

We present our investigations into producing functional cardiovascular tissue: 1) results following the Ross procedure performed using tissue-engineered pulmonary valves, 2) development of a decellularization model for porcine hearts, 3) application of this model to decellularize aortic, pulmonary, mitral and tricuspid valves, 4) recellularization of these heart valves with human umbilical cord endothelial cells in a bioreactor that we constructed ourselves, 5) application of the same model to decellularize whole aortic arches, investigation of the their mechanical characteristics and differences compared with conventional Dacron grafts in vivo.

Results

Tissue-engineered pulmonary valves showed positive clinical results. Our decellularization model and bioreactor was able to almost completely decellularize the heart valves, followed by complete recellularization. Tissue-engineered aortic arches have mechanical characteristics that are very similar to native arches, in contrast to Dacron grafts.

Conclusion

The results presented here suggest considerable potential for tissue engineering in the treatment of cardiovascular pathologies. This positive clinical experience with tissue-engineered pulmonary valves underpins the future significance of this therapeutic approach. However, chronic/long-term in vivo studies are needed in order to effectively verify the results presented here in terms of their clinical relevance to later use in humans.

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Authors and Affiliations

  1. Klinikum Oldenburg AöR, Universitätsklinik für Herzchirurgie, Rahel-Strauss-Str. 10, 26133, Oldenburg, Deutschland

    A. Mashhour MB BCh &  A. Weymann FECTS

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  1. A. Mashhour MB BCh
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Correspondence to A. Weymann FECTS.

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A. Mashhour und A. Weymann geben an, dass kein Interessenkonflikt besteht.

Alle beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethikkommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor. Alle nationalen Richtlinien zur Haltung und zum Umgang mit Labortieren wurden eingehalten, und die notwendigen Zustimmungen der zuständigen Behörden liegen vor.

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Mashhour, A., Weymann, A. Herstellung kardiovaskulären Gewebes aus dezellularisiertem biologischem Material. Z Herz- Thorax- Gefäßchir 31, 350–356 (2017). https://doi.org/10.1007/s00398-017-0158-x

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  • DOI: https://doi.org/10.1007/s00398-017-0158-x

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