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.

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