A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration

Area of Science:

• Cardiovascular Research
• Regenerative Medicine
• Immunology

Background:

• Mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) show synergistic benefits in treating ischemic cardiomyopathy.
• While allogeneic MSCs are immunoevasive, the immune-eluding capacity of CSCs is debated, potentially hindering allogeneic cell combination therapy (ACCT).

Purpose of the Study:

• To investigate the synergistic effects of ACCT on cardiac regeneration and immune response.
• To test the hypothesis that ACCT promotes cardiac repair without inducing adverse immunologic reactions.

Main Methods:

• Göttingen swine with experimental ischemic cardiomyopathy received transendocardial injections of allo-MSCs + allo-CSCs (ACCT), allo-MSCs alone, allo-CSCs alone, or placebo.
• Cardiac function and remodeling were assessed using cardiac magnetic resonance imaging and pressure volume catheterization.
• Immune responses were evaluated through histologic analyses, including markers for mitosis and regulatory T cells.

Main Results:

• ACCT and allo-MSCs significantly reduced cardiac scar size.
• Only ACCT prevented negative left ventricular remodeling and improved systolic function, indicated by an improved end-systolic pressure-volume relation.
• ACCT promoted cardiomyocyte and non-cardiomyocyte proliferation and induced an immunotolerant environment with regulatory T cells, showing absent to low-grade inflammation.

Conclusions:

• ACCT synergistically enhances cardiac regeneration and functional recovery in a swine model of ischemic cardiomyopathy.
• The combination therapy demonstrated a lack of adverse immunologic reactions.
• Clinical translation of ACCT for human patients with chronic ischemic cardiomyopathy is warranted.