Mini hearts are cultivated as trees in Hong Kong and the future of the pharmaceutical industry

These mini hearts simulate what happens to a child's ventricles.

Inside a nursery at Hong Kong's Novoheart headquarters, a series of small glass boxes are holding pea puffed in warm saline. Each pea is a 3D sub-organ of a human being - a miniature version of the organism that simplifies compared to reality.

Among those beans, there is a miniature heart. It has only 1 empty compartment instead of 4 compartments like the heart beating in your chest. But only 1 block is enough for future drug trials.

Ten years and billions of dollars is the average price that pharmaceutical companies pay to research a drug, from the beginning to the end of the product and are allowed to sell in the market. Experimental versions of the drug are likely to cause serious side effects, which often cannot be detected until a real human drug test.

The heart is one of the first places to suffer from such side effects. Therefore, pharmaceutical companies want to find ways to identify problems that new drugs can cause to the heart early. It is the market that Novoheart wants to target, producing miniature hearts in glass cases, for the purpose of testing drugs.

Hearts that are cultivated like trees in Hong Kong will open the future for the pharmaceutical industry.

Miniature hearts respond to drugs in ways very similar to real heart tissue: They increase or decrease the number of beats per minute, beating weaker or stronger. Companies that produce them like Novoheart or American Biosystems (the company that made flat hearts from heart tissue in a lab dish) - can measure these changes and send that data to manufacturers. drug.

From the data, pharmaceutical researchers can predict any potential problems or injuries that may occur in their human trials. Over the past few years, these companies have signed contracts with many of the world's leading pharmaceutical companies, to create such early warning systems.

The idea of ​​using miniature artificial organs to test drugs is not new. But there must be recent biological achievements, we will be able to develop them. One of the biggest difficulties to create artificial heart models, is that the heart cells that are raised outside the body do not want to grow up:

To work, they have to mature, differentiate into different types of cells to form an adult heart. Without that differentiation, they will be protein deficient, where drugs can bind.

At the time that Kevin Costa, co-founder of Novoheart, head of the Cardiology and Cardiovascular Cells Department at Icahn School of Medicine, began pursuing the idea of ​​miniature hearts, new scientists were able to play. Develop a single cell layer on the test plate.

Such 2D heart models can only bend in place, they cannot contract to pump blood like what a real heart collects is doing about 70 times per minute.

To be able to reproduce those beats, scientists have to develop cells in three dimensions. They implanted them into floating floats, so as not to be hindered by flat surfaces. So cells begin to grow and differentiate into different types like in natural heart tissue.

But they still do not work as well as heart tissue. So the next thing scientists do is to put the cells into pieces. Cardiac muscle is like a piece of plywood - consisting of individual cell layers linked in different directions. These layers of cells work together to allow tissue to contract to produce a response to electrical impulses that stimulate it.

However, even when beating like real heart, artificial tissue strips still lack some of the main functions. Costa thinks that if shaped like a ventricle, cardiac tissue can further simulate natural cardiac functions.

However, creating stratified structures into an empty heart compartment requires some real creativity.

Scientists at Novoheart have embedded millions of reprogrammed heart cells from stem cells into a fluid-filled mold with a secret formula containing a number of fibroblasts, cells that help skin heal itself. The mix of cell types will help simulate natural tissues in a better way.

Like Jell-O, they are intertwined into the shape of an empty sphere. Costa says 3D heart tissue is just like a baby's heart, meaning it is smaller than an adult's heart, but they are more responsive than the thin-hearted 2D version of the lab dish.

"We do not fully understand why the hollow sphere reacts more to the actual" heart , "Costa said. 'Is there something from the liquid that is floating inside it? Do cross-forces affect cell growth? We are still unclear, but there is definitely something unique in its shape. It works like a heart, so it was a heart '.

Novoheart's heart is embedded in a solution with a secret formula.

Saying that, it's still not a true heart. For one thing, this model was good enough that a series of pharmaceutical companies began to be interested in using it to test the toxicity of the drug. Moreover, Novoheart is using their miniature hearts as a disease research tool.

They just completed a collaborative study with the pharmaceutical company Pfizer, to develop a heart model of Friedreich's ataxia, a rare but life-threatening neuromuscular disorder. There are approved treatments.

Using cells that carry genetic mutations related to the disease, Novoheart can replicate electrical and muscle problems similar to what happens to a patient's heart. Costa hopes this is only the first step towards creating a library of miniature hearts, fully replicating the heart disease models that help detect new drugs, especially for disorders. can use animal models.

Tara Biosystems is also aiming for that with their 2D hearts. In addition, the company plans to become a platform for personalized drug testing - helping us know how different genetic originating heart cells respond to different treatments. Currently, Tara Biosystems has been able to create 200 new 2D hearts each week, meeting the growing demand of 10 pharmaceutical companies that have signed with them.

Scientists gather data from Novoheart's miniature heart.

Legally, everything is going on schedule. The US Food and Drug Administration (FDA) is currently considering a new safety screening method, aimed at detecting the effects of heart-affecting and life-threatening new drugs.

The system will use both computer simulations and test on the same cell that forms Tara's 2D hearts and Novoheart's 3D heart chamber.

"The FDA itself has realized that the currently widely used trials are not the best trials, and they are looking for alternative solutions , " said Nate Huebsch, a biologist at the University of Washington. is cooperating with start-up Organos to develop microorganisms for drug testing.

Despite standing on the side of a technically competitive competitor, he was impressed with Tara and Novoheart's research results.

'Both companies are driven by the great leaders in the field who have worked for years and are doing the most advanced scientific activities,' Huebsch said. He also emphasized the fact:

"Miniature hearts will not completely replace animal models in the near future. But they can still prevent dangerous drug trials, before they stop a beating heart. the ".