Engineering the maturation of stem cell-derived cardiomyocytes

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Tissue Engineering

Background:

• Maturation of human stem cell-derived cardiomyocytes (hSC-CMs) remains a significant hurdle for broader applications in regenerative medicine and disease modeling.
• Immature hSC-CMs exhibit limited structural and functional properties compared to adult cardiomyocytes, restricting their utility.

Approach:

• This review systematically summarizes diverse strategies employed to enhance hSC-CM maturation.
• Approaches discussed include substrate modification (geometry, stiffness), extracellular matrix optimization, mechanical and electrical stimulation, co-culturing, biochemical regulation, metabolic reprogramming, and advanced 3D constructs (organoids, engineered heart tissue).
• Emphasis is placed on recent advancements and innovative techniques in the field.

Key Points:

• Engineering physical cues like substrate properties and mechanical stretch significantly impacts hSC-CM maturation.
• Biochemical and metabolic regulation offers targeted approaches to guide cardiomyocyte development.
• 3D cardiac constructs and *in vivo* culturing represent promising avenues for achieving more mature and functional hSC-CMs.

Conclusions:

• A multifaceted approach combining various strategies is likely necessary to achieve robust hSC-CM maturation.
• Addressing current limitations and challenges is essential for translating these advancements into clinical applications.
• Future research should focus on optimizing these strategies and understanding their synergistic effects for improved hSC-CM functionality.