Scholarlink

<p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-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 hiPSC-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 an hiPSC-CM maturation medium formulation, designed using a differential evolutionary approach targeting metabolic functionality for iterative optimization. Relative to existing high-performing reference formulations, our medium significantly matured morphology, Ca<sup>2+</sup> handling, electrophysiology, and metabolism, which was further validated by multi-omic screening, for cells in either pure or co-cultured microtissue formats. Together, these findings not only provide a reliable workflow for highly functional hiPSC-CMs for downstream use, but also demonstrate the power of high-dimensional optimization processes in evoking advanced biological function in vitro.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Advanced physiological maturation of human iPSC-derived cardiomyocytes using an algorithm-directed optimization of defined media components

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月31日

查看全文
  • Neal I. Callaghan,
  • Lauren J. Durland,
  • Wenliang Chen,
  • Uros Kuzmanov,
  • Maria Zena Miranda,
  • Yu Ding,
  • Zahra Mirzaei,
  • Ronald G. Ireland,
  • Cristine Reitz,
  • Renée A. Gorman,
  • Erika Yan Wang,
  • Karl 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

摘要

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-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 hiPSC-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 an hiPSC-CM maturation medium formulation, designed using a differential evolutionary approach targeting metabolic functionality for iterative optimization. Relative to existing high-performing reference formulations, our medium significantly matured morphology, Ca2+ handling, electrophysiology, and metabolism, which was further validated by multi-omic screening, for cells in either pure or co-cultured microtissue formats. Together, these findings not only provide a reliable workflow for highly functional hiPSC-CMs for downstream use, but also demonstrate the power of high-dimensional optimization processes in evoking advanced biological function in vitro.