Cardiomyocyte Maturation-the Road is not Obstructed

Area of Science:

• Cardiovascular Biology
• Stem Cell Biology
• Regenerative Medicine

Background:

• Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are a potential therapy for cardiovascular diseases.
• The clinical application of hPSC-CMs is limited by their immature state, characterized by incomplete structural, functional, and metabolic development.
• Cardiomyocyte maturation is a complex biological process involving intricate signaling pathways.

Purpose of the Study:

• To review the structural and functional disparities between immature hPSC-CMs and mature cardiomyocytes.
• To provide a comprehensive overview of current methodologies employed to induce cardiomyocyte maturation.
• To highlight the challenges in achieving an adult-like phenotype in hPSC-CMs.

Main Methods:

• Review of existing literature on cardiomyocyte maturation techniques.
• Analysis of 2D and 3D culture systems for inducing maturation.
• Discussion of factors influencing maturation, including long-term culture, co-culture, small molecules, and biophysical cues.
• Examination of the role of biomaterial surface topography and biophysical cues.

Main Results:

• Significant structural, functional, and metabolic differences exist between hPSC-CMs and adult cardiomyocytes.
• Various methods, including 2D and 3D culturing, small molecules, and biophysical stimuli, can promote cardiomyocyte maturation.
• Current methods struggle to fully replicate the complex signaling networks governing in vivo maturation.
• Combined approaches using biomaterials and biophysical cues show potential for enhanced maturation.

Conclusions:

• Achieving a fully mature, adult-like phenotype in hPSC-CMs remains a significant challenge.
• Understanding and manipulating the signaling pathways involved in maturation are crucial for future therapeutic applications.
• Further research is needed to develop robust protocols for generating clinically relevant, mature hPSC-CMs.