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Reifung von aus pluripotenten Stammzellen gewonnenen Kardiomyozyten und Zukunftsperspektiven für die regenerative Medizin

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Stammzellen

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Zusammenfassung

Aus pluripotenten Stammzellen gewonnene Kardiomyozyten (PSC-CMs) haben ein großes Potenzial als Quelle für Kardiomyozyten, um abgestorbene Zellen bei Herzerkrankungen zu ersetzen (regenerative Medizin), die Pathophysiologie vererbter Herzerkrankungen wie Kardiomyopathie nachzuvollziehen (Krankheitsmodellierung) und die Toxizität neu entwickelter Arzneimittel in vitro zu testen (Arzneimittelforschung). Dank der Fortschritte, die in den letzten zwei Jahrzehnten bei der Gewinnung von PSC-CMs erzielt wurden, können hochgradig gereinigte PSC-CMs mit hoher Ausbeute zur Behandlung von Patienten hergestellt werden. Aufgrund ihrer Unreife, die einem fötalen Stadium ähnelt, ist der Nutzen von PSC-CMs für die Krankheitsmodellierung und die Entdeckung von Medikamenten jedoch noch begrenzt. Daher gewinnt die Reifung von Kardiomyozyten zunehmend an Bedeutung. In diesem Kapitel fassen wir die wichtigsten Merkmale zusammen, die unreife und reife Kardiomyozyten definieren, sowie den Prozess, wie Kardiomyozyten im Herzen reifen. Angesichts der Erkenntnis, dass PSC-CMs nach der Transplantation in Herzen reifer sind, müssen geeignete Umgebungsbedingungen entscheidend für die Reifung sein. Daher werden mögliche Einflussfaktoren wie Zeit (verlängerte Kultur), Kulturumgebungen (z. B. extrazelluläre Matrizen, postnatale Hormone, Veränderungen der Stoffwechselsubstrate und Substratsteifigkeit), interzelluläre Kommunikation (z. B. physikalische Stimulationen und die Auswirkungen benachbarter Nicht-Kardiomyozyten), In-vivo-Reifung und dreidimensionale Kultursysteme untersucht. Am Ende des Kapitels geben wir auch einen Ausblick auf die Verwendung reifer PSC-CMs in der Krankheitsmodellierung, der Arzneimittelforschung und der regenerativen Medizin.

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Abbreviations

AP:

Aktionspotenzial

ARVD/C:

Arrhythmogene rechtsventrikuläre Dysplasie/Kardiomyopathie

BMP:

Morphogenetisches Knochenprotein

Cx43:

Connexin 43

CDK:

Cyclin-abhängige Kinase

DCM:

Dilatative Kardiomyopathie

ES-Zellen:

Embryonale Stammzellen

ECMs:

Extrazelluläre Matrices

FAO:

β-Oxidation von Fettsäuren

hCMPs:

Menschliche Herzmuskel-Patches

hERG:

Menschliches Ether-a-go-go-verwandtes Gen

HCN4:

Hyperpolarisations-aktivierter durch zyklische Nukleotide gesteuerter Kanal 4

iPS-Zellen:

Induzierte pluripotente Stammzellen

LTCCs:

Kalziumkanäle vom L-Typ

MI:

Myokardinfarkt

MHC:

Schwere Myosinkette

NRVMs:

Neonatale ventrikuläre Myozyten der Ratte

PKP2:

Plakophilin-2

PSCs:

Pluripotente Stammzellen

PSC-CMs:

Aus pluripotenten Stammzellen gewonnene Kardiomyozyten

RBM20:

RNA-Bindungsmotiv-Protein 20

RYRs:

Ryanodin-Rezeptoren

SR:

Sarkoplasmatisches Retikulum

SERCA2a:

Kalzium-ATPase 2a des sarkoplasmatischen/endoplasmatischen Retikulums

NCX:

Natrium-Calcium-Austauscher

T-Tubuli:

Transversaltubuli

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Authors and Affiliations

  1. Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan

    Nawin Chanthra & Hideki Uosaki

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  1. Nawin Chanthra
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  1. Departement für Grundlagenwissenschaften, Sulaiman AlRajhi Universität, Al Bukayriyah, Saudi Arabia

    Khawaja H. Haider

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Chanthra, N., Uosaki, H. (2023). Reifung von aus pluripotenten Stammzellen gewonnenen Kardiomyozyten und Zukunftsperspektiven für die regenerative Medizin. In: Haider, K.H. (eds) Stammzellen. Springer, Cham. https://doi.org/10.1007/978-3-031-25378-2_14

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