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Engineering Alignment Has Mixed Effects on Human Induced Pluripotent Stem Cell Differentiated Cardiomyocyte
Nikhith G Kalkunte1, Talia E Delambre1, Sogu Sohn1
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Tissue Engineering. Part A
|March 1, 2023
Summary
Engineered alignment of human induced pluripotent stem cells (hiPSCs) before and during differentiation accelerates cardiomyocyte maturity. This approach improves cell function and mitochondrial structure, advancing cardiac tissue engineering.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Biomaterials Science
Background:
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, limiting their potential.
- Biomimetic substrates promoting cell alignment are explored for hiPSC-CM maturation, but fail to replicate in vivo alignment during differentiation.
- The relationship between cardiomyocyte structure and function necessitates strategies to enhance hiPSC-CM development.
Purpose of the Study:
- To investigate the impact of engineered alignment on hiPSC-CM electrochemical coupling and mitochondrial morphology during differentiation.
- To assess the effects of early-stage alignment on cardiac differentiation and metabolic maturation.
- To explore the potential of combining engineered alignment with other maturation strategies for improved cardiac tissue engineering.
Main Methods:
- Engineered alignment of hiPSCs was implemented before and during cardiac differentiation, starting as early as day 4.
- Optical redox imaging was uniquely applied to monitor metabolic changes during differentiation in heterogeneous cell populations.
- Cardiac-specific markers were used in conjunction with imaging to assess cardiac metabolism and cell subtype differentiation.
Main Results:
- Engineered alignment successfully induced cell alignment in differentiating hiPSCs.
- Alignment promoted differentiation towards the ventricular compact cardiomyocyte subtype and improved electrochemical coupling by day 14.
- The study observed the metabolic shift from glycolysis to oxidative phosphorylation throughout differentiation and noted changes in mitochondrial morphology by day 28.
Conclusions:
- Cellular alignment accelerates hiPSC-CM maturity by enhancing structure-function relationships.
- Early and sustained engineered alignment improves hiPSC-CM electrochemical coupling and drives differentiation.
- Combining engineered alignment with other maturation techniques holds promise for developing mature hiPSC-CMs and advancing cardiac tissue engineering.
