Zusammenfassung
Kardiomyozyten (CMs), die aus humanen induzierten pluripotenten Stammzellen (hiPSCs) gewonnen wurden, sind für die Modellierung von Herz-Kreislauf-Erkrankungen (CVD) sowie für die Entwicklung von Plattformen zur Arzneimittelprüfung weit verbreitet. Darüber hinaus unterstützen vielversprechende Daten aus präklinischen Studien die Vorstellung einer erfolgreichen klinischen Anwendung von hiPSC-CMs in der regenerativen Medizin. Daher ist die detaillierte funktionelle Charakterisierung dieser hiPSC-CMs für die Stammzellforschung von größter Bedeutung, insbesondere wenn eine klinische Umsetzung angestrebt wird. Das Multi-/Mikroelektroden-Array (MEA) bietet ein wertvolles, nicht-invasives Werkzeug zur Untersuchung der elektrophysiologischen Eigenschaften von CMs. Das folgende Kapitel beschreibt den physiologischen und technischen Hintergrund von MEA-basierten Messungen in hiPSC-CMs, einschließlich der Unterschiede und Gemeinsamkeiten zwischen Feldpotenzial- und Aktionspotenzial-Aufzeichnungen. Darüber hinaus fassen wir aktuelle Arbeiten zusammen, die die MEA-Technologie zur Bewertung der medikamenteninduzierten Kardiotoxizität und zur Bewertung der pathophysiologischen Mechanismen, die herzspezifischen Krankheiten zugrunde liegen, eingesetzt haben. Auf der Grundlage von MEA-Daten können Differenzierungsprotokolle optimiert werden, um die Reifung von hiPSC-CMs zu verbessern oder schwere Nebenwirkungen potenzieller antiarrhythmischer Substanzen zu erkennen. Dies wiederum wird dazu beitragen, neue Strategien für die Behandlung von Herz-Kreislauf-Erkrankungen zu entwickeln.
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Abbreviations
- AP:
-
Aktionspotenzial
- APD:
-
Dauer des Aktionspotenzials
- Ca2+:
-
Kalzium
- CIPA:
-
Umfassender In-vitro-Proarrhythmie-Assay
- CMs:
-
Kardiomyozyten
- CSAHI:
-
Konsortium für Sicherheitsbewertung mit menschlichen iPS-Zellen
- CVDs:
-
Kardiovaskuläre Erkrankungen
- ESCs:
-
Embryonale Stammzelle
- FP:
-
Feldpotenzial
- FPDc:
-
Feldpotenzialdauer (korrigiert)
- FRET:
-
Fluoreszenz-Resonanz-Energieübertragung
- hERG:
-
Humanes Ether-a-go-go-verwandtes Gen/spannungsempfindlicher Kaliumkanal
- hiPSCs:
-
Menschliche induzierte pluripotente Stammzelle
- K+:
-
Kalium
- LMNA:
-
Lamin A/C
- MEA:
-
Multi/Mikro-Elektroden-Array
- MYH7:
-
Schwere Myosinkette 7
- Na+:
-
Natrium
- RNA:
-
Ribonukleinsäure
- SCN5A:
-
Natrium-Spannungskanal Alpha-Untereinheit 5
- TBX5:
-
T-Box-Transkriptionsfaktor
- TdP:
-
Torsade-de-Pointes-Tachykardie
- TnnT:
-
TroponinT
- VSO:
-
Spannungsempfindliches optisches System
- WT:
-
Wildtyp
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Kussauer, S., David, R., Lemcke, H. (2023). Mikroelektroden-Arrays: Ein wertvolles Instrument zur Analyse von aus Stammzellen gewonnenen Kardiomyozyten. In: Haider, K.H. (eds) Stammzellen. Springer, Cham. https://doi.org/10.1007/978-3-031-25378-2_1
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