Three-dimensional heart extracellular matrix enhances chemically induced direct cardiac reprogramming

Area of Science:

• Regenerative Medicine
• Cardiovascular Biology
• Biomaterials Science

Background:

• Direct cardiac reprogramming offers a potential therapeutic strategy for cardiac regeneration.
• Chemical reprogramming using small molecules avoids genetic manipulation risks but faces efficiency and maturation challenges.
• The therapeutic efficacy of chemically induced cardiomyocytes (CiCMs) remains largely unexplored.

Purpose of the Study:

• To investigate the impact of a 3D decellularized heart extracellular matrix (ECM) on chemical reprogramming of fibroblasts into cardiomyocytes.
• To assess the maturation, functional properties, and therapeutic potential of CiCMs generated within this 3D ECM.
• To evaluate the utility of this platform for regenerative medicine, disease modeling, and drug screening.

Main Methods:

• Fibroblast reprogramming into cardiomyocytes using small molecules within a 3D decellularized heart ECM.
• Characterization of CiCMs for cardiac marker expression, sarcomeric organization, and electrophysiological properties.
• In vivo assessment of CiCM therapeutic potential in a rat myocardial infarction model.

Main Results:

• The 3D heart ECM significantly enhanced chemical reprogramming efficiency and cardiomyocyte maturation.
• Generated CiCMs displayed improved cardiac marker expression, sarcomeric structure, and electrophysiological function.
• CiCMs demonstrated therapeutic potential in a preclinical model of myocardial infarction.

Conclusions:

• A 3D heart ECM microenvironment effectively promotes chemical cardiac reprogramming and maturation.
• This approach yields functional CiCMs with therapeutic promise for cardiac regeneration.
• The developed platform supports applications in regenerative medicine, disease modeling, and drug discovery.