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Microscale grooves regulate maturation development of hPSC-CMs by the transient receptor potential channels (TRP channels)
Authors:Taoyan Liu  Siyao Zhang  Chenwu Huang  Shuhong Ma  Rui Bai  Yanan Li  Yun Chang  Chenwen Hang  Amina Saleem  Tao Dong  Tianwei Guo  Youxu Jiang  Wenjing Lu  Lina Zhang  Luo Jianwen  Hongfeng Jiang  Feng Lan
Affiliation:1. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

University of Chinese Academy of Sciences, Beijing, China

Contribution: Data curation (lead), Resources (lead);2. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

Contribution: Data curation (equal), Writing - original draft (lead);3. Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China

Contribution: Data curation (equal), Software (equal);4. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

Contribution: Formal analysis (equal), Validation (equal), Writing - original draft (equal);5. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

Contribution: Formal analysis (equal), Validation (equal);6. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

Contribution: Data curation (equal), Validation (equal), Visualization (equal);7. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

Contribution: ​Investigation (equal), Validation (equal);8. Department of Cardiology, Peking University Third Hospital, Beijing, China

Contribution: Data curation (equal), Validation (equal), Visualization (equal);9. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

Contribution: Data curation (equal), Writing - original draft (equal);10. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

Contribution: Data curation (equal), Validation (equal);11. State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, China

Contribution: Formal analysis (equal), Software (equal);12. Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China

Contribution: Data curation (equal), Resources (equal);13. Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing, China;14. Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China

Abstract:The use of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Micro-scaled grooves can promote the maturation of cardiomyocytes by aligning them in order, but the mechanism of cardiomyocytes alignment has not been studied. From the level of calcium activity, gene expression and cell morphology, we verified that the W20H5 grooves can effectively promote the maturation of cardiomyocytes. The transient receptor potential channels (TRP channels) also play an important role in the maturation and development of cardiomyocytes. These findings support the engineered hPSC-CMs as a powerful model to study cardiac disease mechanism and partly mimic the myocardial morphological development. The important role of the TRP channels in the maturation and development of myocardium is first revealed.
Keywords:hPSC-CMs  maturation  microtopography  topographic cues  TRP channels
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