Zusammenfassung
Die Regeneration des Herzens nach einem Myokardinfarkt und bei schwerer Herzinsuffizienz nach einem Myokardinfarkt oder einer dilatativen Kardiomyopathie werden als Kernelement umfassender therapeutischer Strategien zur Verbesserung von Überleben und Lebensqualität diskutiert. Das Kapitel konzentriert sich auf die Entwicklung neuartiger stammzellbasierter Behandlungen für die kardiale Regeneration, da es mehrere Kontroversen über die klinische Wirksamkeit der Zelltherapie bei Patienten nach Myokardinfarkt und Herzinsuffizienz gibt. Bisher wurde postuliert, dass entweder aus menschlichem Knochenmark gewonnene mesenchymale Stammzellen/humane induzierte pluripotente Stammzellen oder deren Sekretome Quellen für neue/verjüngte Herzmuskelzellen sein können. Leider haben Studien des letzten Jahrzehnts keinen klinischen Nutzen der Stammzelltherapie bei Herzinsuffizienz mit verminderter Ejektionsfraktion und uneinheitlicher Besserung nach Implantation von Stammzellen bei Patienten nach Myokardinfarkt gezeigt. Es wird argumentiert, dass in das Myokard injizierte mesenchymale Vorläuferzellen möglicherweise nicht die Antwort auf das schwierige Problem der fortschreitenden Herzinsuffizienz bei Patienten mit Myokardinfarkt und dilatativer Kardiomyopathie sind. Ein derzeit entwickelter mehrgleisiger Ansatz, der auf der gleichzeitigen intramyokardialen Implantation beider Haupttypen von Stammzellen beruht, könnte die Angiogenese, die Gefäßreparatur und die Regeneration induzieren sowie das Überleben der Endothelzellen und die Verjüngung der Herzmuskelzellen verbessern und die Infarktfläche verkleinern. Diese Effekte stehen in direktem Zusammenhang mit der veränderten Expression herzspezifischer Gene, die zur Synthese von Strukturproteinen und Ionenkanälen beitragen, die mitochondriale Belastung verringern, den Zellstoffwechsel unterstützen und die Mikroumgebung einschließlich Fibroblasten, Vorläuferendothelzellen und Herzmuskelzellen verbessern. Wahrscheinlich würde dieser Ansatz das potenzielle Risiko tödlicher Arrhythmien verringern und die Entwicklung einer schweren kontraktilen Dysfunktion verhindern. Obwohl es zahlreiche Belege für die geringe Wirksamkeit der Zelltherapie in Bezug auf das Überleben von Patienten mit Herzinsuffizienz gibt, werden in diesem Kapitel neuartige stammzellbasierte Methoden diskutiert.
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Abbreviations
- AE:
-
Nachteilige Auswirkungen
- AMI:
-
Akuter Myokardinfarkt
- BMMNCs:
-
Mononukleäre Zellen aus dem Knochenmark
- CABG:
-
Koronararterien-Bypass-Transplantation
- CDCs:
-
Aus der Kardiosphäre stammende Zellen
- CMGs:
-
Kardiomyogene Zellen
- CSCs:
-
Kardiale Stammzellen
- CV:
-
Kardiovaskulär
- EF:
-
Ejektionsfraktion
- EPCs:
-
Endotheliale Progenitor(Vorläufer)zellen
- ESCs:
-
Embryonale Stammzellen
- EVs:
-
Extrazelluläre Vesikel
- HF:
-
Herzinsuffizienz
- HFrEF:
-
Herzinsuffizienz mit verminderter Ejektionsfraktion
- HRV:
-
Variabilität der Herzfrequenz
- HSCs:
-
Hämatopoetische Stammzellen
- ISCT:
-
International Society for Cellular Therapy
- iPSCs:
-
Induzierte pluripotente Stammzellen
- LV:
-
Linker Ventrikel
- LVEDV:
-
Linksventrikuläres end-diastolisches Volumen
- LVESV:
-
Linksventrikuläres end-systolisches Volumen
- MACE:
-
Schwerwiegendes unerwünschtes kardiovaskuläres Ereignis
- MI:
-
Myokardinfarkt
- MPCs:
-
Mononukleäre Progenitorzellen
- MSCs:
-
Mesenchymale stromale Zellen
- NYHA:
-
New York Heart Association
- PET:
-
Positronen-Emissions-Tomographie
- PI3K:
-
Phosphoinositid-3-Kinasen
- RCT:
-
Randomisierte klinische Studie
- SAE:
-
Schwerwiegende unerwünschte Wirkung
- SDNN:
-
Standardabweichung der NN-Intervalle
- SPECT:
-
Einzelphotonen-Emissions-Computertomographie
- STEMI:
-
ST-Hebungs-Myokardinfarkt
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Berezin, A.E., Berezin, A.A. (2023). Regeneration des Herzens auf der Grundlage von Stammzellen: Gibt es einen Platz für Optimismus in der Zukunft?. In: Haider, K.H. (eds) Stammzellen. Springer, Cham. https://doi.org/10.1007/978-3-031-25378-2_8
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