Advanced physiological maturation of iPSC-derived human cardiomyocytes using an algorithm-directed optimization of defined media components Article Swipe
Neal I. Callaghan
,
Lauren J. Durland
,
Wenliang Chen
,
Uroš Kuzmanov
,
Maria Zena Miranda
,
Zahra Mirzaei
,
Ronald G. Ireland
,
Erika Yan Wang
,
Karl T. Wagner
,
Michelle M. Kim
,
Julie Audet
,
J. Paul Santerre
,
Anthony O. Gramolini
,
Filio Billia
,
Milica Radisic
,
Seema Mital
,
James Ellis
,
Peter H. Backx
,
Craig A. Simmons
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.10.10.507929
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.10.10.507929
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold tremendous promise for in vitro modeling to assess native myocardial function and disease mechanisms as well as testing drug safety and efficacy. However, current iPSC- CMs are functionally immature, resembling in vivo CMs of fetal or neonatal developmental states. The use of targeted culture media and organoid formats have been identified as potential high-yield contributors to improve CM maturation. This study presents a novel iPSC-CM maturation medium formulation, designed using a differential evolutionary approach targeting metabolic functionality for iterative optimization. Relative to gold-standard reference formulations, our medium significantly matured morphology, Ca 2+ handling, electrophysiology, and metabolism, which was further validated by multiomic screening, for cells in either pure or co-cultured microtissue formats. Together, these findings not only provide a reliable workflow for highly functional iPSC-CMs for downstream use, but also demonstrate the power of high-dimensional optimization processes in evoking advanced biological function in vitro.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.10.10.507929
- https://www.biorxiv.org/content/biorxiv/early/2022/10/13/2022.10.10.507929.full.pdf
- OA Status
- green
- Cited By
- 4
- References
- 88
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4305082644
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4305082644Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2022.10.10.507929Digital Object Identifier
- Title
-
Advanced physiological maturation of iPSC-derived human cardiomyocytes using an algorithm-directed optimization of defined media componentsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-10-13Full publication date if available
- Authors
-
Neal I. Callaghan, Lauren J. Durland, Wenliang Chen, Uroš Kuzmanov, Maria Zena Miranda, Zahra Mirzaei, Ronald G. Ireland, Erika Yan Wang, Karl T. Wagner, Michelle M. Kim, Julie Audet, J. Paul Santerre, Anthony O. Gramolini, Filio Billia, Milica Radisic, Seema Mital, James Ellis, Peter H. Backx, Craig A. SimmonsList of authors in order
- Landing page
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https://doi.org/10.1101/2022.10.10.507929Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2022/10/13/2022.10.10.507929.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2022/10/13/2022.10.10.507929.full.pdfDirect OA link when available
- Concepts
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Induced pluripotent stem cell, Organoid, Workflow, Function (biology), In vitro, In vivo, Cell culture, Biology, Computational biology, Embryonic stem cell, Computer science, Cell biology, Biotechnology, Biochemistry, Database, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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4Total citation count in OpenAlex
- Citations by year (recent)
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2023: 4Per-year citation counts (last 5 years)
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88Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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