A Novel Insight into Endothelial and Cardiac Cells Phenotype in Systemic Sclerosis Using Patient-Derived Induced Pluripotent Stem Cell.
Angiogenesis
Cardiomyocyte
Induced Pluripotent Stem Cells
Systemic Sclerosis
VE-Cadherin
Journal
Cell journal
ISSN: 2228-5806
Titre abrégé: Cell J
Pays: Iran
ID NLM: 101566618
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
03
11
2019
accepted:
26
01
2020
entrez:
26
7
2021
pubmed:
27
7
2021
medline:
27
7
2021
Statut:
ppublish
Résumé
Systemic sclerosis (SSc) is a connective tissue disease associated with vascular damage and multi organ fibrotic changes with unknown pathogenesis. Most SSc patients suffer from defective angiogenesis/vasculogenesis and cardiac conditions leading to high mortality rates. We aimed to investigate the cardiovascular phenotype of SSc by cardiogenic differentiation of SSc induced pluripotent stem cells (iPSC). In this experimental study, we generated iPSC from two diffuse SSc patients, followed by successful differentiation into endothelial cells (ECs) and cardiomyocytes (CMs). SSc-derived EC (SSc-EC) expressed KDR, a nearly EC marker, similar to healthy control-EC (C1-EC). After sorting and culturing KDR+ cells, the resulting EC expressed CD31, a late endothelial marker, but vascular endothelial (VE)-cadherin expression markedly dropped resulting in a functional defect as reflected in tube formation failure of SSc-EC. Interestingly, upregulation of SNAI1 (snail family transcriptional repressor 1) was observed in SSc-EC which might underlie VE-cadherin downregulation. Furthermore, SSc-derived CM (SSc-CM) successfully expressed cardiacspecific markers including ion channels, resulting in normal physiological behavior and responsiveness to cardioactive drugs. This study provides an insight into impaired angiogenesis observed in SSc patients by evaluating
Identifiants
pubmed: 34308570
doi: 10.22074/cellj.2021.7244
pmc: PMC8286459
doi:
Types de publication
Journal Article
Langues
eng
Pagination
273-287Informations de copyright
Copyright© by Royan Institute. All rights reserved.
Déclaration de conflit d'intérêts
There is no conflict of interest in this study.
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