Transcriptomic Analysis of Mineralized Adipose-Derived Stem Cell Tissues for Calcific Valve Disease Modelling
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 25(2024), 4 vom: 14. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Brodeur, Alyssa [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Adipose-derived stromal/stem cells |
|---|
| Anmerkungen: |
Date Completed 26.02.2024 Date Revised 27.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms25042291 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368869474 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368869474 | ||
| 003 | DE-627 | ||
| 005 | 20240229164611.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms25042291 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1309.xml |
| 035 | |a (DE-627)NLM368869474 | ||
| 035 | |a (NLM)38396969 | ||
| 035 | |a (PII)2291 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Brodeur, Alyssa |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Transcriptomic Analysis of Mineralized Adipose-Derived Stem Cell Tissues for Calcific Valve Disease Modelling |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 26.02.2024 | ||
| 500 | |a Date Revised 27.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a RNA sequencing | |
| 650 | 4 | |a adipose-derived stromal/stem cells | |
| 650 | 4 | |a calcific aortic valve disease | |
| 650 | 4 | |a disease modelling | |
| 650 | 4 | |a extracellular matrix | |
| 650 | 4 | |a tissue engineering | |
| 700 | 1 | |a Roy, Vincent |e verfasserin |4 aut | |
| 700 | 1 | |a Touzel-Deschênes, Lydia |e verfasserin |4 aut | |
| 700 | 1 | |a Bianco, Stéphanie |e verfasserin |4 aut | |
| 700 | 1 | |a Droit, Arnaud |e verfasserin |4 aut | |
| 700 | 1 | |a Fradette, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Ruel, Jean |e verfasserin |4 aut | |
| 700 | 1 | |a Gros-Louis, François |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 25(2024), 4 vom: 14. Feb. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:25 |g year:2024 |g number:4 |g day:14 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms25042291 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 25 |j 2024 |e 4 |b 14 |c 02 | ||