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Mini-hearts plate.
Swetha Siva in the lab.
Makoto Hara in the lab.
Scientists in the lab.
Hand-colored scanning electron micrograph (SEM) of heart muscles by Martin Oeggerli (Micronaut).
Novartis mini-hearts plate.
Lucas Goguen in the lab.
Gordon Turner in the lab.
Vipender Singh and Savannah Moore in the lab.
Novartis mini-hearts plate.
Novartis mini-hearts plate.

Organoids such as mini-hearts, mini-brains or mini-kidneys have become possible with the development of induced pluripotent stem cell (iPSC) technology.

Developed by Japanese researcher Shinya Yamanaka, who won the Nobel Prize for this discovery, the process allows scientists to transform conventional cells into stem cells, which can grow into all kinds of other cells.

Work on the mini-heart platform started around 2016 at Novartis, which runs a series of organoid platforms. A cross-functional team of Novartis scientists led by Swetha Siva ...

... and Makoto Hara developed the initial mini-heart platform. The trigger was a project that needed the platform for work on a target that was inaccessible through classical models.

The process to produce mini-hearts – or any other organoid – starts by reverting human skin cells to their embryonic stage with a cocktail of agents. The resulting cells can then be reprogrammed to any other cell type, such as heart muscle cells which form into mini-hearts. Joe Wamstad and his team worked to industrialize the production of the heart cells.

The picture shows a hand-colored scanning electron micrograph (SEM) of heart muscles by Martin Oeggerli (Micronaut). The picture was created in collaboration with Makoto Hara and Lucas Goguen of Novartis Biomedical Research, the University Hospital Basel, the School of Life Sciences and the Fachhochschule Nordwestschweiz.

After this step, the mini-hearts are placed in tiny wells on an assay plate and, using electricity, can be stimulated to beat.

The movement of the cells is recorded to understand the behavior of the mini-hearts. Depending on the compound, the cells beat at different speeds.

Gordon Turner and Lucas Goguen worked with engineering colleagues in Cambridge (Andrew Brady) and San Diego (Scott Hammack) to make the system more robust and to increase throughput.

Turner also collaborated with colleagues in San Diego to capture the data and analyze it with the help of AI.

In 2019, biochemists Vipender Singh and Savannah Moore strengthened the platform by including fibroblast cells to allow mini-hearts to last longer. The platform is far advanced today. After a test run, molecules can be washed out. The mini-hearts can thus be reused after a couple of weeks.

The current version of the platform allows for the automated analysis of a 96-well plate. The next iteration of the platform, which is currently being tested, allows a 384-well plate to be analyzed in under 20 minutes. That is a quantum leap compared to the beginning when one camera was able to record only one well – taking hours.

The platform today also allows researchers to learn more about heart biology. This also helps reduce the need for animal testing.