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Cardiac Spheroids as in vitro Bioengineered Heart Tissues to Study Human Heart Pathophysiology
Published on: January 23, 2021
Developing vasculature and stroma in engineered human myocardium
Kareen L Kreutziger1, Veronica Muskheli, Pamela Johnson
1Center for Cardiovascular Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA.
Tissue Engineering. Part A
|December 29, 2010
Summary
Stromal cells, particularly human marrow stromal cells (hMSCs), are crucial for vascularizing engineered heart tissue by modulating the extracellular matrix (ECM). Pro-angiogenic hMSCs, rich in versican, significantly enhance blood vessel formation and host integration.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Stem Cell Biology
Background:
- Engineered heart tissue requires vascularization for successful engraftment and function.
- Stromal cells and their extracellular matrix (ECM) production are implicated in supporting vascular development.
Purpose of the Study:
- To investigate the role of stromal cells in regulating the angiogenic phenotype of engineered heart tissue.
- To determine if stromal cell-derived ECM modulates endothelial cell organization and vascular network formation.
- To identify specific stromal cell types and ECM components that promote vascularization.
Main Methods:
- Development of scaffold-free patches of human myocardium using human embryonic stem cell-derived cardiomyocytes.
- Co-culture of cardiomyocytes with various stromal cells, including human marrow stromal cells (hMSCs).
- Assessment of endothelial cell organization and vascular network formation in vitro.
- Analysis of ECM composition, specifically versican expression.
- In vivo transplantation of engineered patches onto athymic rat hearts to evaluate vascularization and host integration.
Main Results:
- Human marrow stromal cells (hMSCs) significantly enhanced endothelial cell organization compared to other stromal cells.
- Stromal cells produced abundant ECM components, including fibrillar collagen, hyaluronan, and versican.
- Pro-angiogenic hMSC lines expressed high levels of versican, a proteoglycan known to modulate angiogenesis.
- Transplanted patches with pro-angiogenic hMSCs showed a ~50-fold increase in human vessel development and formed anastomoses with host circulation.
- Chimeric vessels containing erythrocytes were observed, indicating successful integration.
Conclusions:
- Stromal cells play a critical role in supporting the vascularization of engineered human myocardium.
- Differences in ECM synthesis, particularly versican production, contribute to the varying pro-angiogenic abilities of different stromal cell types.
- This study provides an in vitro predictive platform for evaluating stromal cell potential in vascular development for tissue engineering applications.
