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Fabrication of 3D Cardiac Microtissue Arrays using Human iPSC-Derived Cardiomyocytes, Cardiac Fibroblasts, and Endothelial Cells
Published on: March 14, 2021
Human stem cell-based three-dimensional microtissues for advanced cardiac cell therapies.
Maximilian Y Emmert1, Petra Wolint, Nadine Wickboldt
1Swiss Centre for Regenerative Medicine, University of Zurich, Switzerland. maximilian.emmert@usz.ch
Biomaterials
|June 4, 2013
Summary
Generating three-dimensional microtissues (3D-MTs) from various human stem cells offers a promising strategy to improve cardiac stem cell therapy retention and survival. These scaffold-free 3D-MTs demonstrate viability and extracellular matrix production, enhancing potential engraftment.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Cardiovascular Research
Background:
- Cardiac stem cell therapy aims to treat myocardial damage but suffers from low transplanted cell retention.
- Scaffold-free, three-dimensional microtissues (3D-MTs) offer a potential solution to improve cell survival and engraftment.
- Comparing different human stem cell sources for 3D-MT generation is crucial for therapeutic development.
Purpose of the Study:
- To compare the ability of various human stem cell sources to form 3D-MTs.
- To evaluate 3D-MTs based on formation characteristics, proliferation, viability, and extracellular matrix (ECM) production.
- To assess the potential of 3D-MTs as a delivery format for cardiac stem cell therapy.
Main Methods:
- Generated 3D-MTs from human bone marrow-derived mesenchymal stem cells (hBMMSCs), adipose tissue-derived mesenchymal stem cells (hATMSCs), human embryonic stem cell-derived Isl1(+) cardiac progenitors (hESC-Isl1(+) cells), and human induced pluripotent stem cells (hiPSCs) using hanging-drop culture.
- Analyzed 3D-MTs using histology, immunocytochemistry, immunohistochemistry, and flow cytometry.
- Assessed 3D-MT diameter, cell distribution, proliferation activity, viability, and ECM production.
Main Results:
- All tested cell types successfully formed uniform, round-oval shaped 3D-MTs within 3 days.
- Human induced pluripotent stem cell (hiPSC)-derived 3D-MTs showed compact cell formation and rapid ECM production, while hESC-Isl1(+) and hiPSC-derived 3D-MTs maintained higher proliferation activity compared to MSCs.
- All 3D-MTs exhibited >70% viability, with cell-specific ECM production and distribution patterns.
Conclusions:
- Three-dimensional microtissues can be effectively generated in vitro from hESC-derived Isl1(+) cells, hiPSCs, and MSC lines via hanging-drop culture.
- These cell-specific 3D-MTs possess sufficient viability and exhibit immediate ECM formation.
- Pre-transplantation in vitro generation of 3D-MTs represents a promising strategy to enhance cellular engraftment and survival in cardiac repair therapies.
