Dual Function of iPSC-Derived Pericyte-Like Cells in Vascularization and Fibrosis-Related Cardiac Tissue Remodeling In Vitro.
Bioartificial Organs
Cell Differentiation
/ genetics
Endothelial Cells
/ cytology
Extracellular Matrix
/ metabolism
Fibroblasts
/ cytology
Fibrosis
/ genetics
Humans
Induced Pluripotent Stem Cells
/ cytology
Myocardium
/ metabolism
Myocytes, Cardiac
/ cytology
Neovascularization, Pathologic
/ genetics
Pericytes
/ cytology
Sarcomeres
/ genetics
Ventricular Remodeling
/ genetics
cardiac fibroblast
cardiac tissue engineering
iPSC-derived vascular cells
myocardial interstitial fibrosis
pericytes
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
25 Nov 2020
25 Nov 2020
Historique:
received:
15
10
2020
revised:
12
11
2020
accepted:
20
11
2020
entrez:
1
12
2020
pubmed:
2
12
2020
medline:
6
3
2021
Statut:
epublish
Résumé
Myocardial interstitial fibrosis (MIF) is characterized by excessive extracellular matrix (ECM) deposition, increased myocardial stiffness, functional weakening, and compensatory cardiomyocyte (CM) hypertrophy. Fibroblasts (Fbs) are considered the principal source of ECM, but the contribution of perivascular cells, including pericytes (PCs), has gained attention, since MIF develops primarily around small vessels. The pathogenesis of MIF is difficult to study in humans because of the pleiotropy of mutually influencing pathomechanisms, unpredictable side effects, and the lack of available patient samples. Human pluripotent stem cells (hPSCs) offer the unique opportunity for the de novo formation of bioartificial cardiac tissue (BCT) using a variety of different cardiovascular cell types to model aspects of MIF pathogenesis in vitro. Here, we have optimized a protocol for the derivation of hPSC-derived PC-like cells (iPSC-PCs) and present a BCT in vitro model of MIF that shows their central influence on interstitial collagen deposition and myocardial tissue stiffening. This model was used to study the interplay of different cell types-i.e., hPSC-derived CMs, endothelial cells (ECs), and iPSC-PCs or primary Fbs, respectively. While iPSC-PCs improved the sarcomere structure and supported vascularization in a PC-like fashion, the functional and histological parameters of BCTs revealed EC- and PC-mediated effects on fibrosis-related cardiac tissue remodeling.
Identifiants
pubmed: 33255686
pii: ijms21238947
doi: 10.3390/ijms21238947
pmc: PMC7728071
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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