ArticleStem cell research & therapy2024
Cell-based therapies reverse the heart failure-altered right ventricular proteome towards a pre-disease state.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- PRIME-HFrEF Trial: a randomized, double-blind, multi-dose umbilical cord-derived mesenchymal stem cell regimen for heart failure.Signal transduction and targeted therapy · 2026Trial
- Materiobiology-guided regulation of mesenchymal stromal cell fate for aging-related diseases: From basic parameter design to clinical application.Bioactive materials · 2026Review
- Right Heart Failure in Critical and Chronic Care: Current Concepts, Challenges and Mechanical Support Strategies.Medical sciences (Basel, Switzerland) · 2025Review
- Cardiac Development, Cellular Composition and Function: From Regulatory Mechanisms to Applications.Cells · 2025Review
- Hemophilia A: An Ideal Disease for Prenatal Therapy.Prenatal diagnosis · 2025Review
- Mechanism and Treatment of Right Ventricular Failure Due to Pulmonary Hypertension in Children.Children (Basel, Switzerland) · 2025Review
- Contemporary treatment of right ventricular failure.JHLT open · 2025Review
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10 authors.
Funding
Abstract
backgroundCongenital 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.
methodsWe 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.
resultsProteomic 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.
conclusionsOur 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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