[From precursor to reprogrammed cells: evolution of cardiomyoplasty]

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Cardiac Pathophysiology

Background:

• Myocardial infarction (MI) causes significant loss of cardiomyocytes (CM), leading to impaired heart function due to limited endogenous regeneration.
• Current therapeutic strategies aim to restore CM numbers through cell transplantation or stimulating endogenous repair mechanisms.

Purpose of the Study:

• To evaluate various strategies for increasing cardiomyocyte numbers post-MI.
• To identify the most promising approaches for cardiac repair and functional recovery.

Main Methods:

• Review and analysis of preclinical and clinical data on cell transplantation (progenitor/stem cells, pluripotent cells), in situ reprogramming of fibroblasts, and pharmacological stimulation of cardiomyocyte proliferation.
• Assessment of therapeutic efficacy based on cardiomyocyte regeneration, cardiac function improvement (e.g., left ventricular ejection fraction), and scar reduction.

Main Results:

• Cell transplantation shows limited differentiation capacity but offers therapeutic benefits via paracrine effects.
• In situ reprogramming of fibroblasts into cardiomyocyte-like cells and stimulation of endogenous cardiomyocyte proliferation are identified as key strategies.
• Combined approaches involving paracrine-stimulating agents and fibroblast reprogramming show potential for optimal therapeutic outcomes.

Conclusions:

• Strategies focusing on in situ cardiac regeneration, specifically fibroblast reprogramming and cardiomyocyte proliferation, hold significant promise for treating myocardial infarction.
• Optimized therapeutic solutions may involve a combination of approaches to enhance cardiac repair, improve ejection fraction, and reduce infarct scar size.