Cell-based therapies reverse the heart failure-altered right ventricular proteome.

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Proteomics

Background:

• Congenital heart defects can cause right ventricular (RV) pressure overload and heart failure.
• Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs), are explored for restoring heart function.
• These cells are believed to act via paracrine mechanisms to protect against apoptosis and regulate cellular function.

Purpose of the Study:

• To investigate the proteomic response of diseased hearts to different cell-based therapies.
• To compare the efficacy of MSCs and various CPC populations in reversing RV pressure overload-induced proteomic changes.

Main Methods:

• An animal model of RV pressure overload was established using pulmonary artery banding (PAB).
• Mesenchymal stromal cells (MSCs) and three types of CPCs (nCPCs, cCPCs, ES-CPCs) were injected into the RV free wall.
• Proteomic analysis using liquid chromatography and tandem mass spectrometry was performed on RV tissues, followed by systems biology and bioinformatics analysis.

Main Results:

• Pulmonary artery banding significantly altered the RV proteome, affecting 5.97% of identified proteins.
• Mesenchymal stromal cell therapy reversed 72% of the PAB-altered proteome, followed by nCPCs (54%), ES-CPCs (52%), and cCPCs (39%).
• Cell therapy demonstrated a decrease in predicted adverse cardiac effects and affected the non-altered RV proteome minimally.

Conclusions:

• Mesenchymal stromal cells, ES-CPCs, and nCPCs effectively reversed the pressure overload-induced proteomic alterations in the RV.
• Cell-based therapies show significant potential for improving RV function post-pressure overload by partially restoring the cardiac proteome.