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Combining genome and tissue engineering for next-generation human biomimetics.

Eric K N Gähwiler¹, Valery L Visser¹, Melanie Generali¹

¹Institute for Regenerative Medicine (IREM), University of Zurich, Schlieren 8952, Switzerland.

Stem Cells Translational Medicine

|November 19, 2025

Summary

This summary is machine-generated.

Researchers developed a new method using human-induced pluripotent stem cells (hiPSCs) to create isogeneic cardiac fibroblast-like cells (iCFs). Gene-edited iCFs enable the creation of advanced human tissue-engineered matrices (hTEMs) with tailored composition and mechanical properties.

Keywords:

cardiac fibroblasts extracellular matrix gene-editing human induced pluripotent stem cells tissue engineering

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Area of Science:

Biomaterials Science
Stem Cell Biology
Regenerative Medicine

Background:

Cardiovascular implant tissue engineering traditionally uses primary human cells, facing challenges like donor variability and limited cell lifespan.
A robust alternative cell source is needed to overcome limitations in generating human tissue-engineered matrices (hTEMs).

Purpose of the Study:

To establish a novel differentiation protocol for human-induced pluripotent stem cells (hiPSCs) into isogeneic cardiac fibroblast-like cells (iCFs).
To engineer iCFs for modulating extracellular matrix (ECM) composition and mechanical properties in hTEMs.
To lay the foundation for next-generation tissue engineering applications in cardiovascular implants.

Main Methods:

Developed animal sera-free, chemically defined differentiation protocol for hiPSCs to iCFs.
Utilized gene-editing to overexpress specific ECM and ECM-related proteins in iCFs.
Analyzed iCF and iCF-derived hTEM characteristics via morphology, ECM deposition, transcriptomics, proteomics, and biaxial mechanical testing.

Main Results:

hiPSC-derived iCFs demonstrated similarity to primary human cardiac fibroblasts in morphology, ECM deposition, and global transcriptomics.
Gene-edited iCFs allowed modulation of ECM composition, with increased collagen and elastic fiber assembly proteins observed in derived hTEMs.
iCF-derived hTEMs exhibited enhanced mechanical functionality, including increased collagen function due to improved crosslinking and maturation.

Conclusions:

Successfully generated a novel, robust cell source (gene-edited iCFs) from hiPSCs for cardiovascular tissue engineering.
Demonstrated the ability to engineer hTEMs with tailored composition and improved mechanical properties using gene-edited iCFs.
Established a foundation for developing next-generation tissue-engineered cardiovascular implants with enhanced functionality.