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Clinical translation of stem cell therapies for heart disease requires electrical integration of transplanted cardiomyocytes. Generation of electrically matured human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) is critical for electrical integration. Here, we found that hiPSC-derived endothelial cells (hiPSC-ECs) promoted the expression of selected maturation markers in hiPSC-CMs. Using tissue-embedded stretchable mesh nanoelectronics, we achieved a long-term stable map of human three-dimensional (3D) cardiac microtissue electrical activity. The results revealed that hiPSC-ECs accelerated the electrical maturation of hiPSC-CMs in 3D cardiac microtissues. Machine learning–based pseudotime trajectory inference of cardiomyocyte electrical signals further revealed the electrical phenotypic transition path during development. Guided by the electrical recording data, single-cell RNA sequencing identified that hiPSC-ECs promoted cardiomyocyte subpopulations with a more mature phenotype, and multiple ligand-receptor interactions were up-regulated between hiPSC-ECs and hiPSC-CMs, revealing a coordinated multifactorial mechanism of hiPSC-CM electrical maturation. Collectively, these findings show that hiPSC-ECs drive hiPSC-CM electrical maturation via multiple intercellular pathways.
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This content will become publicly available on December 1, 2026
AI-guided laser purification of human iPSC-derived cardiomyocytes for next-generation cardiac cell manufacturing
Current methods for producing cardiomyocytes from human induced pluripotent stem cells (hiPSCs) using 2D monolayer differentiation are often hampered by batch-to-batch variability and inef!cient puri!cation processes. Here, we introduce CM-AI, a novel arti!cial intelligence-guided laser cell processing platform designed for rapid, label-free puri!cation of hiPSC-derived cardiomyocytes (hiPSC-CMs). This approach signi!cantly reduces processing time without the need for chronic metabolic selection or antibody-based sorting. By integrating real-time cellular morphology analysis and targeted laser ablation, CM-AI selectively removes non-cardiomyocyte populations with high precision. This streamlined process preserves cardiomyocyte viability and function, offering a scalable and ef!cient solution for cardiac regenerative medicine, disease modeling, and drug disco
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- Award ID(s):
- 2026049
- PAR ID:
- 10640852
- Publisher / Repository:
- Communications Biology NPJ
- Date Published:
- Journal Name:
- Communications Biology
- Volume:
- 8
- Issue:
- 1
- ISSN:
- 2399-3642
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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