Zusammenfassung
Die Ergebnisse adulter Stammzelltherapien am Herzen waren in der Summe ernüchternd. Über parakrine Effekte lassen sich nur sehr begrenzte Funktionsverbesserungen nach Myokardinfarkt erzielen, und eine substanzielle Bildung neuen Herzmuskels konnte nicht nachgewiesen werden. Interessant erscheint unterdessen die Möglichkeit, Bindegewebszellen des Herzens und einer Infarktnarbe direkt zu Kardiomyozyten umzuprogrammieren. Aufgrund nichtabschätzbarer Sicherheitsrisiken und der bisher sehr geringen Effizienz liegt die klinische Umsetzung allerdings bestenfalls noch in weiter Ferne. Große Fortschritte wurden im Gegensatz dazu bereits auf dem Gebiet der seit 2007 verfügbaren induzierten pluripotenten Stamm(iPS)-Zellen erzielt. Neuartige Differenzierungstechnologien erlauben damit nun erstmals die Herstellung der für eine klinische Zelltherapie notwendigen sehr großen Mengen an Herzmuskelzellen. Ob sich allerdings mit der Injektion solcher Zellen in das geschädigte Herz substanzielle Funktionsverbesserungen erzielen lassen, oder ob z. B. eine bereits existierende Infarktnarbe diese unmöglich macht, wird sich erst in den kommenden Jahren in geeigneten präklinischen Großtiermodellen zeigen. Auch gilt es, Risiken iPS-Zellen-basierter Therapien am Herzen, einschließlich Tumorbildung und transplantatinduzierter Arrhythmien, auszuschließen. Nach derzeitigem Stand der Forschung sind erste Phase-I-Studien zu iPS-Zellen-basierten kardialen Therapien durchaus für die kommenden 5 Jahre zu erwarten. Möglicherweise ist jedoch letztendlich der technisch schwierigere komplette Ersatz der Infarktnarbe durch vaskularisierten Herzmuskel, der über das Tissue-Engineering hergestellt wurde, die vielversprechendere Methode.
Abstract
The results of a variety of clinical trials that applied adult stem cells to the heart have been disappointing. Functional improvement after myocardial infarction was typically very limited and based on paracrine effects, whereas no substantial generation of new heart muscle could be demonstrated. Meanwhile, much more interest is directed towards the concept of direct in vivo reprogramming of cardiac fibroblasts; however, due to uncertain safety risks and the so far very low efficiency, clinical translation is still a long way off. In contrast, major progress has already been achieved in the field of induced pluripotent stem cells (iPSC), which became available in 2007. For the first time novel differentiation technologies now allow the generation of the large amounts of cardiomyocytes that will be required for clinical cell therapy. Whether the straightforward injection of these cells into an impaired heart will result in substantial functional improvement or whether for instance an already existing infarct scar may prevent this, remains to be investigated in suitable preclinical large animal models. Additionally, the potential risks of iPSC-based cardiac therapy, including tumor formation and transplant-induced arrhythmias, need to be addressed. Considering the current state of the art, first phase 1 clinical studies on iPSC-based heart repair can be expected within the next 5 years; however, it is possible that ultimately complete substitution of the infarct scar by tissue engineered vascularized heart muscle, which is technically more challenging, is the more promising approach.
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U. Martin und A. Haverich geben an, dass kein Interessenkonflikt besteht.
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Martin, U., Haverich, A. Myokardiales Tissue-Engineering. Z Herz- Thorax- Gefäßchir 31, 200–205 (2017). https://doi.org/10.1007/s00398-016-0119-9
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DOI: https://doi.org/10.1007/s00398-016-0119-9
Schlüsselwörter
- Herzinfarkt
- Herzmuskel
- Zell- und gewebebasierte Therapie
- Induzierte pluripotente Stammzellen
- Zelltransdifferenzierung