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Updated: Jan 24, 2026

Generation of First Heart Field-like Cardiac Progenitors and Ventricular-like Cardiomyocytes from Human Pluripotent Stem Cells
Published on: June 19, 2018
Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors
Jianhua Zhang1,2, Ran Tao3, Katherine F Campbell4,5
1Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53705, USA. jz2@medicine.wisc.edu.
Insights
Researchers developed a new method to create human cardiac fibroblasts (hPSC-CFs) from human pluripotent stem cells (hPSCs). These lab-grown cells mimic native cardiac fibroblasts, offering a valuable tool for heart disease research and regenerative medicine.
Area of Science:
- Cardiovascular Biology
- Stem Cell Differentiation
- Fibroblast Research
Background:
- Cardiac fibroblasts (CFs) are crucial for heart function and disease, but obtaining sufficient human CFs is challenging.
- Human pluripotent stem cells (hPSCs) offer a renewable source, yet efficient differentiation into CFs remains undescribed.
Purpose of the Study:
- To establish an efficient method for generating human cardiac fibroblasts (hPSC-CFs) from hPSCs.
- To characterize the properties of hPSC-CFs and compare them to native CFs.
Main Methods:
- Sequential modulation of Wnt and FGF signaling pathways to guide hPSC differentiation.
- Generation of second heart field progenitors that differentiate into hPSC-CFs.
- Characterization of hPSC-CFs via morphology, gene expression, and functional assays.
Main Results:
- hPSC-CFs successfully generated and exhibited characteristics similar to native CFs, including morphology, gene expression, and extracellular matrix production.
- hPSC-CFs showed myofibroblast transformation in response to TGFβ1 and angiotensin II.
- hPSC-CFs displayed a more embryonic phenotype compared to fetal and adult CFs.
- Co-culture of hPSC-CFs with cardiomyocytes altered cardiomyocyte electrophysiology.
Conclusions:
- hPSC-CFs represent a viable and renewable cell source for studying cardiac fibroblast biology.
- These cells hold significant potential for cardiac disease research, drug discovery, and regenerative therapies.
Abstract:
Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties of the cardiomyocytes compared to co-culture with dermal fibroblasts. The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration.
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