Heart

Heart tissue model

Cardiovascular diseases like heart attacks and heart failure are among the leading causes of death worldwide. The heart is the vital organ for the circulation of blood throughout the body. Developing a 3D model to understand the causes and mechanisms of these diseases will facilitate development of therapeutic treatments. Bioprinted cardiac tissue models generated from stem cells can be matured in vitro to understand cardiomyocyte functionality under various stimulations to mimic disease conditions.

Aim

The aim of following project was to develop heart tissue models using human induced pluripotent stem cell (iPSC) derived cardiac aggregates (cells were kindly provided by Research Groups of Dr. R. Zweigerdt and Dr. U. Martin from the Hannover Medical School, Germany) for 3D bioprinting in CELLINK® LAMININK 521 bioink.  The bioprinted model was cultured for up to three weeks to evaluate the functionality of cardiomyocytes by monitoring the beating of the cells within the constructs.

 

CELLINK Products Used

  • CELLINK® LAMININK 521
  • BIO X

Printing a heart with heart cells

Bioprinting of cardiac tissue model was performed using CELLINK LAMININK 521 and human iPSC-derived cardiac aggregates. These models can be utilized to investigate cardiomyocyte maturation, drug screening, identifying drug targets, and cardiac regeneration.

 

 

In this video, CELLINK LAMININK 521 is bioprinted into the shape on a heart. The cardiomyocyte aggregates were mixed with the bioink at 40 million cells/ml of bioink.

 

 

Beating cells at Day 7

The video demonstrates contraction of the 3D bioprinted cardiac tissues after only one week of culture. The cardiomyocytes within the aggregates integrated into and proliferated in the CELLINK LAMININK 521.

 

 

The brightfield video, obtained with a 10X objective, show the stretched out cardiomyocyte sheet attaching to the CELLINK LAMININK 521 and pulling the bioink with each contraction is evidence of a supportive 3D hydrogel environment. Hence, the CELLINK LAMININK 521 environment encouraged cell proliferation, re-organization, attachment, and functionality/metabolism.

 

 

Cardiomyocyte functionality

After three weeks of culture, the bioprinted cardiac tissue model demonstrated intracellular mobilization of calcium of live cardiac aggregates within the CELLINK LAMININK 521. This was assayed by a fluorescent calcium indicator.

 

 

The incremental green flashes from each aggregate correlate to the flux of calcium during cardiomyocyte contraction. This can be seen in the video, recorded with a 10X objective. Synchronized influx, or green flashes, of some aggregates is an indication of increase cell-cell interaction and communication within the tissue model.

 

 

Conclusion

Bioprinted heart tissue models will enable understanding of cardiovascular disease and advancement in therapeutic discoveries.