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Vascular Perfusion of Implanted Human Engineered Cardiac Tissue
Kareen L K Coulombe1, Charles E Murry2
1Division of Engineering, Biomedical Engineering, Brown University, Providence, RI 02912.
Summary
Engineered heart tissue patches show increased blood vessel density but sluggish flow after myocardial infarction repair. Further vascular engineering is needed for effective blood supply to implanted cardiomyocytes.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Tissue Engineering
Background:
- Myocardial infarction (heart attack) necessitates regeneration of cardiac muscle tissue.
- Successful cardiac regeneration requires survival and integration of transplanted human cardiomyocytes.
- A robust vascular network is crucial for nourishing implanted cardiomyocytes in engineered cardiac tissues.
Purpose of the Study:
- To develop a method for assessing vascular perfusion in engineered human cardiac tissue grafts within the host heart.
- To evaluate the vascularization and blood flow dynamics in scaffold-free engineered cardiac tissue patches.
- To determine the suitability of current engineered grafts for supporting transplanted cardiomyocytes post-myocardial infarction.
Main Methods:
- Co-culture of human embryonic stem cell-derived cardiomyocytes (hESC-CMs), human endothelial cells, and human stromal cells to create scaffold-free engineered tissue patches.
- Development of a perfusion method compatible with confocal microscopy for imaging graft vasculature.
- Histological analysis to assess lumen structure density and confocal microscopy for 2D/3D vascular reconstruction and flow assessment.
Main Results:
- Engineered tissue patches demonstrated a substantial density of lumen structures, indicating successful prevascular network formation.
- Confocal microscopy revealed that despite high vascular density, blood flow within the graft vasculature remained sluggish.
- The developed perfusion method allowed for detailed imaging and reconstruction of the graft's vascular architecture.
Conclusions:
- Scaffold-free engineered cardiac tissue patches can form dense vascular networks.
- Current vascularization strategies are insufficient to achieve physiological blood flow levels required for transplanted cardiomyocytes.
- Significant advancements in arterial remodeling and vascular engineering are necessary for effective cardiac tissue regeneration after myocardial infarction.
