AI Article Synopsis
- Congenital heart defects can cause right ventricular (RV) pressure overload, leading to heart failure, prompting research into cell-based therapies like mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) for restoring function.
- In a study, juvenile rats underwent pulmonary artery banding to induce RV pressure overload, followed by the injection of different cell types, with results analyzed using advanced protein profiling techniques.
- The findings showed that MSC therapy significantly reversed changes in RV proteins caused by pressure overload, outperforming other cell types, indicating the potential effectiveness of these therapies in cardiac recovery.
Article Abstract
Background: Congenital heart defects can lead to right ventricular (RV) pressure-overload and heart failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) have been studied clinically as options to restore heart function in disease states. Many studies have indicated these cells act through paracrine mechanisms to prevent apoptosis, promote cellular function, and regulate gene/protein expression. We aimed to determine the proteomic response of diseased hearts to cell therapy.
Methods: We utilized a juvenile rat model of RV pressure overload created by banding the pulmonary artery (PAB). Two weeks post-banding, bone marrow-derived mesenchymal stromal cells (MSCs) and 3 populations of CPCs (nCPCs, cCPCs, ES-CPCs) were delivered to the RV free wall. RV function and cellular retention were measured for four weeks post-injection, at which point hearts were extracted and the RV was excised for liquid chromatography and tandem mass spectrometry. Resulting RV proteomes were compared and analyzed using systems biology and bioinformatics.
Results: Proteomic profiling identified 1156 total proteins from the RV, of which 5.97% were significantly changed after PAB. This disease-altered proteome was responsive to cellular therapy, with 72% of the PAB-altered proteome being fully or partially reversed by MSC therapy. This was followed by nCPCs (54%), ES-CPCs (52%), and cCPCs (39%). Systems biology and bioinformatics analysis showed MSC, nCPC, or ES-CPC cell therapy is associated with a decrease in predicted adverse cardiac effects. We also observed an effect of cell therapy on the non-altered RV proteome, however, this was associated with minor predicted pathological endpoints.
Conclusions: Our data indicate MSCs, ES-CPCs, and nCPCs significantly reverse the PAB-altered proteome towards a pre-disease state in our animal model. These results indicate cell-based therapies show promise in improving RV function after pressure overload through partial restoration of the disease-altered cardiac proteome.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11559167 | PMC |
| http://dx.doi.org/10.1186/s13287-024-04009-3 | DOI Listing |
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