Miniature hearts: Heart organoids with their own immune systems

© MHH Hannover, Elisa Mohr; Christian Bär
Heart organoids are functional miniature heart structures that can beat spontaneously or be controlled through electrical stimulation, similarly to a pacemaker.

In recent years, there have been some major advances in cancer treatments, largely due to the development of new immunotherapies. In particular, this includes treatments using monoclonal antibodies and cell therapies such as CAR-T cells, which directly target tumor cells. However, it has been shown that these treatments — much like “conventional” cancer treatments that use anthracylines or receptor tyrosine kinases — can often have cardiotoxic properties and lead to heart failure. On the one hand, the new treatments are a blessing, as they are allowing more and more patients to overcome cancer; on the other hand, the cardiotoxicity of the treatments, which sometimes only becomes apparent years later, is posing an increasingly serious clinical problem.

 

The potential cardiotoxicity of a new immunotherapy or cell therapy agents cannot be sufficiently predicted or simulated in conventional cell cultures due to the necessary complexity. In order to solve this issue, scientists at the Hannover Medical School and Fraunhofer ITEM have established a new complex heart organoid model that more effectively mimics the properties of the natural human heart during its (patho-)physiological development. The research team has already produced the first functioning organoids. They consist of cardiomyocytes, cardiac fibroblasts, endothelial cells derived from induced pluripotent stem cells (hiPSC), and stem cells obtained from adipose tissue. These create functional miniature heart structures that can beat spontaneously or be controlled through electrical stimulation, similarly to a pacemaker. Disease modeling approaches have shown that the heart organoids’ contractility can be influenced medicinally and that administering conventional chemotherapeutics leads to a cardiotoxic contractile imbalance.

 

The next step will be to supplement these organoids with another cell type — designer immune cells derived from stem cells. These cells will provide the miniature hearts with an immune system, making it possible for scientists to model and test the cardiotoxicity of new immunotherapies and cell therapies in the future.

Contact

Christian Bär

Contact Press / Media

Prof. Dr. Christian Bär

Manager of the Working Group on Regenerative Cardiology

Phone +49 511 5350-120

Nico Lachmann

Contact Press / Media

Prof. Dr. Nico Lachmann

Manager of the Working Group on IMMUNITY / Head of Attract Group “IMMUNITY – designer cells: novel immune cell platforms for health research”

Phone +49 511 5350 380