Chamber-Specific Decellularized Extracellular Matrices Differentially Modulate Cardiomyocyte Subtypes to Drive...

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Stem Cell Biology

Background:

• Decellularized extracellular matrix (dECM) retains native tissue cues for biomaterial applications.
• Regional variations within an organ's ECM are poorly understood but crucial for tissue engineering.
• Induced pluripotent stem cell-derived cardiomyocyte (CM) subtypes offer potential for engineered heart tissues (EHTs).

Purpose of the Study:

• To investigate the chamber-specific effects of ventricular (vtdECM) and atrial (atdECM) dECMs on engineered heart tissue (EHT) formation.
• To compare the influence of vtdECM and atdECM on the maturation and function of distinct cardiomyocyte (CM) subtypes.
• To explore the impact of encapsulation timing on CM maturation within different dECM environments.

Main Methods:

• Proteomic analysis to characterize vtdECM and atdECM composition.
• Co-culture of induced pluripotent stem cell-derived CM subtypes with chamber-specific dECMs.
• Assessment of CM maturation, function, and gene expression.
• Evaluation of the effects of early versus late CM encapsulation.

Main Results:

• Proteomic analysis revealed distinct protein profiles for vtdECM and atdECM.
• Ventricular CMs showed enhanced maturation and function in vtdECM.
• Atrial CMs exhibited limited responsiveness to ECM composition, despite transcriptomic changes.
• Encapsulation timing modulated structural maturation (early) and calcium handling (late).

Conclusions:

• Chamber-specific dECM composition significantly impacts subtype-specific cardiomyocyte maturation and function in EHTs.
• Developmental timing of encapsulation acts synergistically with ECM cues to regulate CM development.
• These findings provide a foundation for designing more physiologically accurate engineered heart tissues.