Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells

Area of Science:

• Regenerative Medicine
• Biotechnology
• Cardiovascular Research

Background:

• Heart transplantation is limited by donor organ availability.
• Severe heart failure necessitates alternative therapeutic strategies.
• Tissue engineering offers a promising avenue for cardiac repair.

Purpose of the Study:

• To develop a cell sheet-based tissue-engineering technology for fabricating human cardiac tissue.
• To create vascularized, transplantable cardiac grafts using human induced pluripotent stem cell-derived cardiomyocytes.
• To evaluate the in vivo survival, maturation, and functionality of engineered cardiac tissue.

Main Methods:

• Human induced pluripotent stem cells (iPSCs) were differentiated into cardiomyocytes to create cardiomyocyte sheets.
• Layered cardiomyocyte sheets were transplanted onto nude rats, employing a multi-step procedure to enhance thickness and vascularization.
• Engineered cardiac grafts with integrated vessels were ectopically transplanted into rats by connecting to host vasculature.

Main Results:

• Fabricated human cardiac tissue exhibited spontaneous beating and a cardiac muscle-like structure with vascularization.
• Transplanted cells demonstrated in vivo proliferation and maturation.
• Multi-step transplantation successfully created significantly thicker cardiac tissues.
• Ectopically transplanted grafts survived and maintained cardiac function.

Conclusions:

• Functional human cardiac tissue can be successfully fabricated using cell sheet technology and iPSC-derived cardiomyocytes.
• The developed tissue-engineering approach enables the creation of vascularized, transplantable cardiac grafts.
• This technology holds potential as a novel treatment for severe heart failure, addressing donor limitations.