Key result
Human cardiac stromal primitive cells cultured on decellularized ECM from failing hearts upregulated pro-remodeling cytokines and oxidative stress molecules compared to normal heart ECM.
Why the study?
Adverse cardiac remodeling alters extracellular matrix signaling, which can interfere with the phenotype balance of resident cardiac stromal primitive cells.
Does culture on decellularized ECM from failing hearts alter the balance between angiogenic and fibrotic signals in human cardiac stromal primitive cells compared to normal ECM?
Does culture on decellularized ECM from failing hearts alter the balance between angiogenic and fibrotic signals in human cardiac stromal primitive cells compared to normal ECM?
The pathological microenvironment of remodeling ECM from failing hearts shifts resident cardiac stromal primitive cells toward a pro-fibrotic and anti-angiogenic phenotype, suggesting caution in using non-healthy decellularized myocardium for tissue engineering.
Failing heart ECM may drive stromal pro-remodeling signaling; leaves open in vivo relevance and therapeutic targeting.
Cardiac adverse remodeling is characterized by biological changes that affect the composition and architecture of the extracellular matrix (ECM). The consequently disrupted signaling can interfere with the balance between cardiogenic and pro-fibrotic phenotype of resident cardiac stromal primitive cells (CPCs). The latter are important players in cardiac homeostasis and can be exploited as therapeutic cells in regenerative medicine. Our aim was to compare the effects of human decellularized native ECM from normal (dECM-NH) or failing hearts (dECM-PH) on human CPCs. CPCs were cultured on dECM sections and characterized for gene expression, immunofluorescence, and paracrine profiles. When cultured on dECM-NH, CPCs significantly upregulated cardiac commitment markers (CX43, NKX2.5), cardioprotective cytokines (bFGF, HGF), and the angiogenesis mediator, NO. When seeded on dECM-PH, instead, CPCs upregulated pro-remodeling cytokines (IGF-2, PDGF-AA, TGF-β) and the oxidative stress molecule H2O2. Interestingly, culture on dECM-PH was associated with impaired paracrine support to angiogenesis, and increased expression of the vascular endothelial growth factor (VEGF)-sequestering decoy isoform of the KDR/VEGFR2 receptor. Our results suggest that resident CPCs exposed to the pathological microenvironment of remodeling ECM partially lose their paracrine angiogenic properties and release more pro-fibrotic cytokines. These observations shed novel insights on the crosstalk between ECM and stromal CPCs, suggesting also a cautious use of non-healthy decellularized myocardium for cardiac tissue engineering approaches.
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Belviso et al. (2020) studied Heart Failure. Decellularized extracellular matrix from failing hearts (dECM-PH) vs. Decellularized extracellular matrix from normal hearts (dECM-NH) was evaluated on Gene expression, immunofluorescence, and paracrine profiles. Human cardiac stromal primitive cells cultured on decellularized ECM from failing hearts upregulated pro-remodeling cytokines and oxidative stress molecules compared to normal heart ECM.
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