Cited by 46Pluripotent Stem Cells ResearchCardiac electrophysiology and arrhythmiasTissue Engineering and Regenerative Medicine

Functional isolation, culture and cryopreservation of adult human primary cardiomyocytes

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Zhou, Bingying, Shi, Xun, Tang, Xiaoli, Zhao, Quanyi, Wang, Le, Yao, Fang, Hou, Yongfeng, Wang, Xianqiang +5 more·2022·Signal Transduction and Targeted Therapy

Abstract

Cardiovascular diseases are the most common cause of death globally. Accurately modeling cardiac homeostasis, dysfunction, and drug response lies at the heart of cardiac research. Adult human primary cardiomyocytes (hPCMs) are a promising cellular model, but unstable isolation efficiency and quality, rapid cell death in culture, and unknown response to cryopreservation prevent them from becoming a reliable and flexible in vitro cardiac model. Combing the use of a reversible inhibitor of myosin II ATPase, (-)-blebbistatin (Bleb), and multiple optimization steps of the isolation procedure, we achieved a 2.74-fold increase in cell viability over traditional methods, accompanied by better cellular morphology, minimally perturbed gene expression, intact electrophysiology, and normal neurohormonal signaling. Further optimization of culture conditions established a method that was capable of maintaining optimal cell viability, morphology, and mitochondrial respiration for at least 7 days. Most importantly, we successfully cryopreserved hPCMs, which were structurally, molecularly, and functionally intact after undergoing the freeze-thaw cycle. hPCMs demonstrated greater sensitivity towards a set of cardiotoxic drugs, compared to human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Further dissection of cardiomyocyte drug response at both the population and single-cell transcriptomic level revealed that hPCM responses were more pronouncedly enriched in cardiac function, whereas hiPSC-CMs responses reflected cardiac development. Together, we established a full set of methodologies for the efficient isolation and prolonged maintenance of functional primary adult human cardiomyocytes in vitro, unlocking their potential as a cellular model for cardiovascular research, drug discovery, and safety pharmacology.

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Authors
Zhou, B., Shi, X., Tang, X., Zhao, Q., Wang, L., Yao, F., Hou, Y., Wang, X., Feng, W., Wang, L., Sun, X., Wang, L., & Hu, S.
Affiliations
Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Hu, Shengshou
Venue
Signal Transduction and Targeted Therapy
Published
2022-07-27
Volume
7
Issue
1
Pages
254-254
ISSN
2059-3635 (ISSN-L)
OpenAlex
W4288176088
Cited by
46
References
74
Citations by year
2026: 13 · 2025: 13 · 2024: 9 · 2023: 9 · 2022: 2
FWCI
2.69
Type
journal article
Language
en
Open access
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (20211, 81700337, 82070287)
  • Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2021-1-I2M-006)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
cardiomyocyte isolation, cryopreservation, blebbistatin, myosin II inhibition, cardiomyocyte culture, cardiomyocyte viability, mitochondrial respiration, hiPSC-derived cardiomyocytes, single-cell transcriptomics, cardiac electrophysiology, safety pharmacology, in vitro cardiac models
MeSH terms
Adult, Cell Differentiation, Cell Survival, Humans, Cryopreservation, Myocytes, Cardiac, Induced Pluripotent Stem Cells

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