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Early Vascular Cells Improve Microvascularization Within 3D Cardiac Spheroids
Isaree Pitaktong1, Cecillia Lui2, Justin Lowenthal1
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
Tissue Engineering. Part C, Methods
|December 14, 2019
Summary
Engineered cardiac tissues benefit from early vascular cells (EVCs), which promote microvascular formation and improve spheroid contraction in 3D cardiac microtissues.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Cardiovascular Research
Background:
- Engineered cardiac tissues face challenges with oxygen and nutrient diffusion due to limited vascularization in 3D constructs.
- Human induced pluripotent stem cell (hiPSC)-derived early vascular cells (EVCs) show potential for organizing vascular networks within hydrogels.
- Improving vascularization is crucial for developing clinically relevant engineered cardiac tissues.
Purpose of the Study:
- To investigate the impact of introducing hiPSC-derived EVCs into 3D cardiac microtissue spheroids.
- To assess the effects of EVCs on microvascular formation, cell distribution, and cardiac function within spheroids.
- To compare the efficacy of EVCs against human umbilical vein endothelial cells (HUVECs) in cardiac spheroid development.
Main Methods:
- Co-culturing hiPSC-derived cardiomyocytes (CMs) with cardiac fibroblasts (FB) and either HUVECs or EVCs for 72 hours.
- Forming mixed cell spheroids using three different cell ratio groups: CM:FB:HUVEC (70:15:15), CM:FB:EVC (70:15:15), and CM:FB:EVC (40:15:45).
- Analyzing vascularization, cell distribution patterns, and cardiac function (contraction rate) of the formed spheroids.
Main Results:
- EVC-containing spheroids exhibited enhanced microvasculature with novel endothelial organization morphologies compared to HUVEC spheroids.
- Cardiomyocytes showed a more uniform distribution in EVC spheroids, unlike the core-shell distribution observed in control spheroids.
- Spheroids incorporating EVCs demonstrated an increased contraction rate compared to control spheroids.
Conclusions:
- Triculture of CMs, FBs, and EVCs within cardiac spheroids effectively promotes microvascular formation.
- The inclusion of EVCs enhances cardiac spheroid contraction, indicating improved cardiac function.
- hiPSC-derived EVCs represent a promising cell source for vascularizing engineered cardiac tissues.
