[재미있는 과학] Making a 2mm micro-heart with human cells to test the effectiveness of new drugs

A total of 12,567,325 animals were used for experiments in Korea for five years from 2017. Animal experiments are mainly conducted to check different effects and side effects before making medicines for human use. However, since the animals used in the experiment are biologically different from humans, the reaction shown by injecting the drug into the animal may not be the same as the reaction of humans. Even if a drug is found to be safe in animal studies, there is no guarantee that it will be safe in humans.

Recently, as the awareness that animals have the right to live as animals (animal rights) spreads, the scientific community is making various efforts to reduce animal testing and find alternative testing methods.

Organoids made from human cells

As animal cells are different from humans, if it is not possible to properly check the response to drugs, it is possible to experiment using human cells. By making small (mini) organs out of human cells. Organs made for this purpose are called organoids. It is a combination of two words ‘Organ’ (organ) and ‘Oid’ (similar). In 2009, Professor Hans Clevers from Utrecht University in the Netherlands announced the possibility to the world by creating small intestines with mouse stem cells.

Stem cells are needed to make organoids. Stem cells are cells that have the ability to differentiate into all tissue cells. These stem cells begin to form organs in earnest when their path is set as a specific organ cell. For example, if stem cells become skin cells, they grow naturally creating a unique skin structure by dividing into the epidermis (tissue that covers the surface of the skin) and the dermis (tissue beneath the epidermis).

Organoids are made using these characteristics of stem cells. The principle is simple, but it is not easy to make it as big as a real organ. Additionally, it is very difficult to grow organs without a proper digestive system to nourish them. Because of this, organoids that have been successfully made so far are very small in size. Last year, a study was published in the international journal Cell that succeeded in making cardiac organoids for the first time in the world. This heart was only 2 mm in diameter. Although it is small, it beats 60 to 100 times a minute, playing the role of a heart. In the same year, tear gland organoids with a diameter of 0.2 mm made actual tears.

Recently, research on how to grow large organoids is also being carried out. A study on how to make pea-sized brain organoids with human stem cells and transplant them into young mice to increase their size was published in the international journal Nature on the 13th of last month. As the mice grew, the transplanted brains also grew and actually functioned. According to the research team, the cells that are grown after transplantation into the brains of mice are significantly larger than the brain cells (nerve cells) that are grown only in the incubator. However, this method has a limitation as it requires another animal experiment to make organoids.

Like semiconductors, ‘organic chips’ are also being tested

Research is also being done on how to make ‘long life chips’ like semiconductors. It’s called ‘Lab on a chip’, and it’s a technology that makes parts that function the same as human organs. Place organoid cells on a small piece and allow the body to metabolize artificially there, see the reaction.

This method became known to the world in 2010 when Harvard University’s Bisimetic Engineering Institute created for the first time a 3cm ‘Lung on a chip’ that reproduced the relationship between lung cells and capillaries. Rather than implementing all the functions of an organ, we focus on reproducing a specific phenomenon or seeing how a drug reacts in a specific area. By engineering a structure and placing cells or organoids on top of it.

As the heart pumps, blood circulates throughout the body and supplies oxygen and nutrients. When the blood circulates and uses all the oxygen it has, it goes to the lungs to receive new oxygen. The lungs supply new oxygen to this very blood. Exchange of oxygen and carbon dioxide takes place between the thin and long capillaries between the lung cells. Lung cells give oxygen to the capillaries, and capillaries send carbon dioxide to the lung cells. The blood in the capillaries receives new oxygen and returns to the heart.

Rung on a Chip is a chip structure modeled after the shape of a lung. Furthermore, lung cells and capillary cells are cultured to make organoids. For these lung and capillary cells to function normally, the heart must pump and circulate blood, but this chip has an artificial vacuum pump instead of a real heart. This vacuum pump forces blood to flow through the capillaries, causing the lungs to expand and contract repeatedly, like breathing in and then breathing out. Then, the lungs and capillary cells work normally as in the human body. In this situation, if a specific drug is injected, it is possible to see how the lung cells and capillaries react.

Starting with step-on-a-chip, various chips are being developed. A ‘blinking eye on a chip’, made from a curved cornea like a real eye and designed to make the eyelid blink, has also been developed. These prosthetic eyelashes blink 12 times per minute just like real eyelashes, but you can adjust the number of blinks. After making the eyelid condition similar to that of dry eye syndrome, it can be used to check the effect of a new drug or to test contact lenses.

stricter animal testing

Animal testing is getting stricter. Since 2016, the sale of cosmetics developed through animal testing has been banned. Animal testing for research has also become more challenging. In order for researchers to be able to carry out experiments with animals, they must write an experiment plan and obtain the approval of the Animal Experimentation Ethics Committee. In particular, veterinarians belonging to the Animal Experimentation Ethics Committee continue to check the condition of the animals. If the animal used in the experiment feels excessive pain or is seriously ill, it is recommended to stop the experiment and proceed with ‘humane termination (euthanasia)’.

It takes time for new technologies to be used seriously, which is why animal testing may still be necessary in our society. Because you can’t give a new drug candidate to a real person without at least a guarantee of safety. But humans, as always, will find new solutions.