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Updated: Oct 27, 2025
Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Advanced Glycation End Products Impair Cardiac Atrial Appendage Stem Cells Properties
Lize Evens1, Ellen Heeren1, Jean-Luc Rummens1,2
1BIOMED, UHasselt-Hasselt University, Agoralaan, 3590 Diepenbeek, Belgium.
Insights
Advanced glycation end products (AGEs) negatively impact cardiac stem cells (CASCs) survival, proliferation, and migration. These harmful effects, mediated partly by the receptor for AGEs (RAGE), suggest caution for stem cell therapy post-myocardial infarction.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Stem Cell Science
Background:
- Myocardial infarction (MI) causes significant loss of cardiomyocytes.
- Stem cell therapy, using cardiac atrial appendage stem cells (CASCs), is a potential regenerative approach.
- Elevated advanced glycation end products (AGEs) in the cardiac environment may impair stem cell efficacy.
Purpose of the Study:
- To investigate the impact of AGEs on CASCs properties in vitro.
- To determine the role of the receptor for AGEs (RAGE) in mediating AGEs' effects on CASCs.
Main Methods:
- CASCs were exposed to varying concentrations of AGEs (50–400 µg/mL) for 72 hours.
- Cell survival, proliferation, migration, and apoptosis were assessed.
- The effect of a RAGE inhibitor (FPS-ZM1) was evaluated.
Main Results:
- AGEs exposure significantly reduced CASCs survival, proliferation, and migration.
- Apoptosis in CASCs increased in a dose-dependent manner with AGEs exposure.
- RAGE inhibition partially mitigated the detrimental effects of AGEs on CASCs.
Conclusions:
- AGEs exert time- and concentration-dependent negative effects on CASCs in vitro.
- These effects are partially mediated through RAGE activation.
- Further research is needed to evaluate anti-AGEs therapies in the context of stem cell transplantation after MI.
Background:
During myocardial infarction (MI), billions of cardiomyocytes are lost. The optimal therapy should effectively replace damaged cardiomyocytes, possibly with stem cells able to engraft and differentiate into adult functional cardiomyocytes. As such, cardiac atrial appendage stem cells (CASCs) are suitable candidates. However, the presence of elevated levels of advanced glycation end products (AGEs) in cardiac regions where CASCs are transplanted may affect their regenerative potential. In this study, we examine whether and how AGEs alter CASCs properties in vitro.
Methods And Results:
CASCs in culture were exposed to ranging AGEs concentrations (50 µg/mL to 400 µg/mL). CASCs survival, proliferation, and migration capacity were significantly decreased after 72 h of AGEs exposure. Apoptosis significantly increased with rising AGEs concentration. The harmful effects of these AGEs were partially blunted by pre-incubation with a receptor for AGEs (RAGE) inhibitor (25 µM FPS-ZM1), indicating the involvement of RAGE in the observed negative effects.
Conclusion:
AGEs have a time- and concentration-dependent negative effect on CASCs survival, proliferation, migration, and apoptosis in vitro, partially mediated through RAGE activation. Whether anti-AGEs therapies are an effective treatment in the setting of stem cell therapy after MI warrants further examination.
