Transcriptomic Analysis of Mineralized Adipose-Derived Stem Cell Tissues for Calcific Valve Disease Modelling.
Alyssa BrodeurVincent RoyLydia Touzel-DeschênesStéphanie BiancoArnaud DroitJulie FradetteJean RuelFrançois Gros-LouisPublished in: International journal of molecular sciences (2024)
Calcific aortic valve disease (CAVD) is characterized by the fibrosis and mineralization of the aortic valve, which leads to aortic stenosis and heart failure. At the cellular level, this is due to the osteoblastic-like differentiation of valve interstitial cells (VICs), resulting in the calcification of the tissue. Unfortunately, human VICs are not readily available to study CAVD pathogenesis and the implicated mechanisms in vitro; however, adipose-derived stromal/stem cells (ASCs), carrying the patient's specific genomic features, have emerged as a promising cell source to model cardiovascular diseases due to their multipotent nature, availability, and patient-specific characteristics. In this study, we describe a comprehensive transcriptomic analysis of tissue-engineered, scaffold-free, ASC-embedded mineralized tissue sheets using bulk RNA sequencing. Bioinformatic and gene set enrichment analyses revealed the up-regulation of genes associated with the organization of the extracellular matrix (ECM), suggesting that the ECM could play a vital role in the enhanced mineralization observed in these tissue-engineered ASC-embedded sheets. Upon comparison with publicly available gene expression datasets from CAVD patients, striking similarities emerged regarding cardiovascular diseases and ECM functions, suggesting a potential link between ECM gene expression and CAVDs pathogenesis. A matrisome-related sub-analysis revealed the ECM microenvironment promotes the transcriptional activation of the master gene runt-related transcription factor 2 ( RUNX2 ), which is essential in CAVD development. Tissue-engineered ASC-embedded sheets with enhanced mineralization could be a valuable tool for research and a promising avenue for the identification of more effective aortic valve replacement therapies.
Keyphrases
- aortic valve
- aortic stenosis
- aortic valve replacement
- extracellular matrix
- ejection fraction
- transcatheter aortic valve replacement
- gene expression
- stem cells
- transcatheter aortic valve implantation
- transcription factor
- single cell
- left ventricular
- heart failure
- cardiovascular disease
- nlrp inflammasome
- rna seq
- genome wide
- cell therapy
- prognostic factors
- newly diagnosed
- induced apoptosis
- coronary artery disease
- signaling pathway
- mesenchymal stem cells
- bone marrow
- oxidative stress
- type diabetes
- pi k akt
- endothelial cells
- atrial fibrillation
- peritoneal dialysis
- heat shock protein