A novel method to align cells in a cardiac tissue-like construct fabricated by cell sheet-based tissue engineering

Area of Science:

• Biotechnology
• Regenerative Medicine
• Cardiovascular Research

Background:

• Fabricating cardiac tissue from human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) is promising for regenerative medicine.
• A key challenge is achieving cardiomyocyte alignment to optimize force generation in engineered tissues.

Purpose of the Study:

• To develop and evaluate a novel, scaffold-free method for aligning hiPS-CMs in a cardiac tissue-like construct.
• To assess the in vitro and in vivo characteristics of stretched vs. non-stretched hiPS-CM sheets.

Main Methods:

• A unidirectional stretching method was applied to hiPS-CM sheets cultured on a temperature-responsive dish and silicone surface.
• Co-culture with human adipose-derived stem cells was used for in vitro morphology evaluation.
• Stretched and non-stretched hiPS-CM sheets were transplanted into athymic rats for in vivo analysis.

Main Results:

• Stretching significantly elongated the hiPS-CM sheets compared to controls.
• Immunohistology confirmed unidirectional cardiomyocyte alignment in stretched sheets, versus random alignment in controls.
• Transplanted stretched sheets maintained unidirectional myocardial fiber orientation with higher intensity than controls.

Conclusions:

• Unidirectional stretching of hiPS-CM sheets is a simple and effective scaffold-free method for creating aligned cardiac tissue constructs.
• This technique enhances cardiomyocyte alignment and orientation intensity, crucial for functional cardiac tissue engineering.
• The method holds potential for advancing the development of functional cardiac grafts.