DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulatein vitroHuman Cardiac Pathophysiology

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F20%3A00073002" target="_blank" >RIV/00159816:_____/20:00073002 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/20:00116091

Result on the web

<a href="https://www.frontiersin.org/articles/10.3389/fbioe.2020.00535/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fbioe.2020.00535/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fbioe.2020.00535" target="_blank" >10.3389/fbioe.2020.00535</a>

Result language

angličtina

Original language name

DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulatein vitroHuman Cardiac Pathophysiology

Original language description

Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by the lack of functional dystrophin. DMD is associated with progressive dilated cardiomyopathy, eventually leading to heart failure as the main cause of death in DMD patients. Although several molecular mechanisms leading to the DMD cardiomyocyte (DMD-CM) death were described, mostly in mouse model, no suitable human CM model was until recently available together with proper clarification of the DMD-CM phenotype and delay in cardiac symptoms manifestation. We obtained several independent dystrophin-deficient human pluripotent stem cell (hPSC) lines from DMD patients and CRISPR/Cas9-generated DMD gene mutation. We differentiated DMD-hPSC into cardiac cells (CC) creating a human DMD-CC disease model. We observed that mutation-carrying cells were less prone to differentiate into CCs. DMD-CCs demonstrated an enhanced cell death rate in time. Furthermore, ion channel expression was altered in terms of potassium (Kir2.1 overexpression) and calcium handling (dihydropyridine receptor overexpression). DMD-CCs exhibited increased time of calcium transient rising compared to aged-matched control, suggesting mishandling of calcium release. We observed mechanical impairment (hypocontractility), bradycardia, increased heart rate variability, and blunted beta-adrenergic response connected with remodeling of beta-adrenergic receptors expression in DMD-CCs. Overall, these results indicated that our DMD-CC models are functionally affected by dystrophin-deficiency associated and recapitulate functional defects and cardiac wasting observed in the disease. It offers an accurate tool to study human cardiomyopathy progression and test therapiesin vitro.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

20800 - Environmental biotechnology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY

ISSN

2296-4185

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

2020

Country of publishing house

CH - SWITZERLAND

Number of pages

19

Pages from-to

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UT code for WoS article

000548398600001

EID of the result in the Scopus database

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