Cardiac-Derived ECM Microspheres for Enhanced hiPSC-CMs Maturation

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Cardiovascular Research

Background:

• Phenotypic immaturity of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hinders their use in disease modeling and cardiac regeneration.
• Existing culture platforms struggle to provide a physiologically relevant microenvironment for cardiomyocyte maturation.

Purpose of the Study:

• To develop a novel biomaterial platform for enhanced hiPSC-CM maturation.
• To investigate the efficacy of cardiac extracellular matrix (ECM) microspheres in supporting hiPSC-CM development.

Main Methods:

• Fabrication of reproducible, heart tissue-derived cardiac ECM microspheres with a porous 3D architecture.
• Culture of various cell types, including hiPSC-CMs, on ECM microspheres.
• Assessment of hiPSC-CM maturation through gene expression, calcium handling, sarcomere organization, and protein expression.

Main Results:

• ECM microspheres supported attachment and proliferation of multiple cell types, including hiPSC-CMs.
• Compared to 2D cultures, ECM microspheres significantly enhanced hiPSC-CM maturation, evidenced by upregulated cardiac genes (ACTA2, TNNT2, GJA1), improved calcium cycling, and synchronized transients.
• Long-term culture (up to 8 months) on ECM microspheres promoted hiPSC-CM maturation, with enhanced sarcomere alignment, α-actinin expression, contractile function, connexin 43 (CX-43) expression, and binucleation.

Conclusions:

• Cardiac ECM microspheres provide a scalable, bioactive 3D platform for long-term hiPSC-CM culture and maturation.
• This system holds promise for advancing cardiac disease modeling, drug screening, and cardiac tissue engineering applications.