Modelling cardiac fibrosis using three-dimensional cardiac microtissues derived from human embryonic stem cells

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Tissue Engineering

Background:

• Cardiac fibrosis is a common pathway in many heart diseases.
• Existing in vitro models fail to replicate the complex human heart environment.
• A novel 3D cardiac sphere platform is presented to better model the human heart.

Purpose of the Study:

• To develop a functional in vitro model for cardiac fibrosis.
• To investigate the role of mesenchymal stem cells (MSCs) in cardiac fibrosis.
• To create a platform for evaluating pro-fibrotic agents.

Main Methods:

• Constructed a 3D cardiac microtissue platform using human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and MSCs.
• Induced cardiac fibrosis using transforming growth factor-β1 (TGF-β1).
• Analyzed tissue structure, gene expression, and cellular changes.

Main Results:

• MSCs improved cardiac microtissue organization and function.
• MSCs differentiated into fibroblasts, which transdifferentiated into myofibroblasts upon TGF-β1 treatment.
• The model exhibited key fibrotic features: collagen deposition, cardiomyocyte apoptosis, and mitochondrial damage.

Conclusions:

• The 3D cardiac microtissue platform is a valuable tool for studying cardiac fibrosis.
• This model can manifest and evaluate pro-fibrotic effects of various agents.
• It represents a significant advancement for predicting drug-induced cardiac fibrosis and studying pathological changes.