The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1 activation

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Cardiovascular Research

Background:

• Myocardial infarction (MI) is a leading global cause of death.
• Cardiac progenitor cells (CPCs) show therapeutic potential in early clinical trials for MI.
• Notch1 signaling is crucial for cardiac development and CPC function.

Purpose of the Study:

• To evaluate the therapeutic benefit of CPCs delivered via Jagged1-mimicking peptide (RJ)-functionalized self-assembling peptide (SAP) hydrogels in a rat MI model.
• To investigate the effect of RJ-functionalized hydrogels on CPC behavior in vitro and in vivo.

Main Methods:

• Functionalization of SAP hydrogels with RJ peptide.
• In vitro evaluation of CPC gene expression, proliferation, and growth factor production within hydrogels.
• Assessment of Notch1 activation in CPCs cultured in hydrogels of varying concentrations.
• In vivo study in a rat MI model using cell-loaded RJ-functionalized hydrogels.

Main Results:

• Notch1 activation in CPCs was dependent on hydrogel stiffness and synergistically increased with RJ presence.
• RJ-mediated Notch1 activation differentially regulated CPC gene expression, proliferation, and growth factor production in vitro.
• RJ hydrogel delivery of CPCs improved acute retention and cardiac function in rats post-MI compared to controls.

Conclusions:

• SAP hydrogels functionalized with RJ peptide can modulate Notch1 signaling in CPCs.
• RJ-functionalized SAP hydrogels offer a promising strategy for enhancing CPC-based cardiac repair after myocardial infarction.