A New Method to Stabilize C-Kit Expression in Reparative Cardiac Mesenchymal Cells

Area of Science:

• Cardiovascular Research
• Cell Biology
• Regenerative Medicine

Background:

• Cell therapy, particularly using c-kit sorted cells, shows promise for improving cardiac function.
• Maintaining c-kit expression during cell passaging is a significant challenge, potentially limiting therapeutic efficacy.
• Cardiac mesenchymal cells (CMCs) are a potential cell source for cardiac repair.

Purpose of the Study:

• To develop an improved method for isolating c-kit positive (c-kit(pos)) cells that preserves c-kit expression during passaging.
• To compare the therapeutic efficacy of slowly adherent (SA) CMCs versus rapidly adherent (RA) CMCs in a post-myocardial infarction model.
• To investigate the potential mechanisms underlying the observed therapeutic effects of SA CMCs.

Main Methods:

• Cardiac mesenchymal cells (CMCs) were isolated from wild-type mice based on differential adherence to polystyrene.
• Rapidly adherent (RA) and slowly adherent (SA) CMC populations were identified and sorted for c-kit expression.
• SA and RA CMCs were administered via percutaneous delivery in a mouse model of myocardial infarction.

Main Results:

• SA CMCs exhibited significantly higher c-kit expression and a more pronounced endothelial marker profile compared to RA CMCs.
• SA CMCs, but not RA CMCs, significantly improved cardiac function following myocardial infarction compared to vehicle treatment.
• SA CMC treatment was associated with increased vascular density in the infarct border zone, suggesting a pro-vasculogenic effect.

Conclusions:

• A novel method utilizing differential adherence properties effectively isolates CMCs with enhanced c-kit expression maintenance.
• Slowly adherent (SA) CMCs demonstrate superior therapeutic efficacy in improving cardiac function post-infarction compared to rapidly adherent (RA) CMCs.
• The improved cardiac function mediated by SA CMCs may be linked to their endothelial phenotype and pro-vasculogenic potential, though the precise role of c-kit expression requires further investigation.