Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering

Area of Science:

• Tissue Engineering
• Regenerative Medicine
• Biotechnology

Background:

• Three-dimensional (3D) tissue construction using pre-isolated cells is crucial for advancing medicine and drug discovery.
• Cell sheet engineering offers high cell density and transplantation efficiency, enabling applications in regenerative medicine.
• Native tissues rely on capillary networks for nutrient and oxygen supply, a critical factor for engineered tissue viability.

Purpose of the Study:

• To develop a method for constructing thick, vascularized 3D tissues by layering cell sheets.
• To investigate the spontaneous formation of vascular networks within cell sheets.
• To establish a perfusion system for maintaining the viability of multi-layered cell sheets.

Main Methods:

• Innovative layering of multiple cell sheets to create 3D tissue constructs.
• Investigation of endothelial cell behavior within cell sheets to form vascular networks.
• Development and testing of two vascular bed types: femoral muscle-based and synthetic collagen gel-based.
• Utilizing bioreactor systems for perfusion and maintenance of engineered tissues.

Main Results:

• Endothelial cells within cell sheets spontaneously formed in vivo-like capillary networks.
• Both developed vascular bed types successfully perfused culture medium through the cell sheet vascular networks.
• The perfusion system enabled the survival of 12-layer cell sheets, demonstrating successful vascularization.
• Functional vascularized 3D tissues were produced using cell sheet engineering and bioreactor systems.

Conclusions:

• Layering cell sheets with integrated vascular networks is a viable strategy for creating thick, functional 3D tissues.
• The developed vascular bed systems are critical for perfusing engineered tissues and ensuring cell viability.
• This approach holds significant promise for applications in regenerative medicine and drug discovery research.