Monday , November 23 2020

Spare Parts from the Laboratory – News Knowledge: Medicine & Psychology



Who would have thought that the intestine looked good? If the doctor Hans Clevers tells his work, then the cells of the intestinal mucus appear bright, orange and blue on the computer screen, streaks, red and green wrinkles wrinkle. As a painter with brushes, the researcher at the Utrecht Hubrecht Institute created works created in the stem cell lab: human organs in miniature.

Cleverek and his colleagues depict colorful pictures, helping one day to stop liver damage, heal the sick lung and inflamed lips. Mini-organs offer unprecedented opportunities for disease detection and drug testing.

For this, human mini-organs grow in mice while researchers see color tumors growing, infecting cell structures with viruses, bacteria, or parasites. One day, hopefully, laboratory specimens can serve as a substitute for organs.


Artificial human organs. (Video: Youtube / EPOfilms)

Technically, mini-organs are called organoids, and doctors increasingly associate with bio-scientists and material scientists, molecular biologists, and computer scientists to grow more and more mature specimens.

In Utrecht, it is particularly noticeable that the different disciplines and research branches complement each other. "Many scientists today enter the organoid to better understand the origin of human life and simulate and overcome the disease," says Clevers, a physician and immunologist.

Miniatures from a stem cell

The Hubrecht Development Biological Institute hangs in the lobby of a giant white body of cardboard boxes in which curious visitors can get involved, and in large shop windows historical animal embryos and old microscopes can relax. Behind him a red-red minister appears on the screen, looks like a valuable painting of an art gallery. Hubrecht Art – Hubrecht art – is in large letters beside it.

On the first floor, Hans Clevers reports on the first brushwork of his research. He is considered to be one of the great artists of Organoid researchers who for the first time years succeeded in breeding only laboratory ministries. The small intestine grew from a single stem cell, which at that time had many colleagues, such as magic or neglect. "Nobody wanted to believe us first," Clever remembers.

At the same time, too many dogmas were broken by the doctor: biologists were so convinced that the mature human body contained scarcely stem cells in the gut, completely unknown. Second, they agreed that body cells outside the human body would die in a few days.

But now Clever said they found a whole bunch of adult stem cells in the gut. In addition, he has been able to have mini-organs from the surviving stem cells for months. Twice, reviewers of Nature Magazine rejected her article, Clevers reported. In 2009, the study finally published the era of organoid research.

Hans Clevers points to a mini-Därmchens cell on a computer, looks like a starburst, which is hollow. In other images, the organoids of the intestinal organs are marked in green and red, sometimes in more colors than if someone painted a colored strip on a black paper. Markers help researchers observe the behavior of stem cells under the microscope and gather messenger cocktails that inhibit growth of organoids.

Above all, Clevers must embed stem cells into a gel to form a three-dimensional structure. In Clever's lab, tanks of such piles were resting in the incubators, all of which were Smartie's size.

What is spectacular in microscopic color images looks better than a powder with the naked eye. The organoids are so small that they can only be recognized as black dots. How will these little things ever help the patients?

The defective gene leads to mutations

To explain this, Hans Clevers likes to talk about Fabian and his colleague, Kors van der Ent. The pulmonologist works near the Hubrecht Institute of the Wilhelmina Children's Hospital and met with Fabian when the boy was 16 years old, a clever, athletic, cheerful teenager.

In fact. If there had not been such a condition, the cystic fibrosis, which clogged the trachea with a viscous mucous membrane, prevented him from breathing, threatening to abduct his future. A girl who passed away at Kors van der Ent died under her hands as a young medical assistant. This can not happen again. Kors van der Ent decided to make the miniseries from Fabians' intestinal tissue.

Cystic fibrosis is the most common hereditary illness and often leads to death in the first decades of life. One patient's gene is defective, more than 2,000 different mutations occur in cystic fibrosis patients, some of which are common, others are very rare. For some years now there are new drugs on the market that can help some patients with frequent gene mutations.

The genetic defect occurs twice a year worldwide

Or rather, doctors know which common gene mutations the drugs work for because they have been tested. However, other gene mutations are so rare that expensive tests are not worth the pharmaceutical industry. For example, Fabian suffers from a genetic defect that has been known to him twice a year: with him and with his aunt.

In general, doctors have to test new drugs in animal experiments and clinical trials. Kors van der Ent, however, chose a shortcut: his colleagues raised the miniature lungs of the boy and raised new labs in the laboratory. "Mini Fabian's intestines reacted very well to therapy," says Kors van der Ent. As a result, the pulmologist prescribed the drug for the patient. After a few days Fabian's slowdown died, soon he was playing hockey again. "Fabian was finally able to enjoy the life of a teenager," says Kors van der Ent.

Test the active ingredients in the mini-organs

But the doctor was not alone with the young patient. Rather, he and Hans Clevers would respond to one of the most urgent questions of organoid research: does the mini-organs really depict the internal functioning of the real organs? In a Europe-wide study, I would like to look at the mini-dummies of 500 cystic fibrosis patients.

Finally, scientists Georgios Vlachogiannis of the London Cancer Institute reported in the journal Science that the minimal organizations of cancer patients were very reliably alert to the success or failure of chemotherapy. "Excellent study," says Hans Clevers appreciated. For example, PhD student Else Driehuis works on cancer therapies. He is currently conducting an investigation into the testing of medicines for patients with mini-organs in the headache and neck cancer patients and to compare patient treatment.

Clevers has long established a tissue bank, and not far from his institute, nonprofit start-up staff can use mini-organs to test drugs at their own projects or at pharmaceutical companies. Jasper Mullender, one of the starting group leaders, puts thick gloves before frozen specimens are pulled out of a silver cooler tank. Minus 180 degrees Celsius stores thousands of mini organs here. In small plastic containers arranged in white plastic boxes, organic materials are scattered in the healthy and diseased tissues of the patients, especially in cancer patients and cystic fibrosis.

Better understanding of parasites and malaria

And new-type patterns are constantly added. In Hans Clevers's laboratory, staff members are now bred to have a break to remember the latest results. From the pancreas, organoids and bladder, lungs and cervical glands were obtained.

And oh, yeah, the mini-organs of the hepatocytes are particularly complicated, and one of the staff members will soon announce the successful Cell fame. One of the new organoids of hepatocytes appears as a red art work at the Institute's lobby.

Clevers, however, is looking for black and white microfilms this time, but pale organoids of hepatocytes carry very special loads: Clevers employees are infected with the parasites by the structures. "So far, we did not know which pathos of the pathogen are going through the liver. Now we can observe that organoids," says the doctor. Researchers also introduced malaria parasites into the mini-organs in order to better understand the course of the disease.

Some genetic defects have already corrected them

It is as if Hans Clevers originally had painted a rough sketch, and his colleagues and other researchers now depict the details of the organoid's internal functioning. Not far from the Hubrecht Institute lies the Principals of Máxima, opposite the Center for Cancer, located opposite the Wilhelmina Hospital, where the pulmonary therapist Kors van der Ent operates. The transition with colored glass windows connects buildings as if the architecture of clinics wanted to draw attention to the fact that the research of organoids converges here.

At the Princes Máxima Center, Florijn Dekkers is launching his laptop and introducing images that are almost as colorful as the external transition. Years ago, the stem cell researcher developed a drug test for mucositis patients such as Fabian; In the meantime, it is rather about organoids related to breast cancer. On her screen, blue, red and green, spectacular three-dimensional images show subtle junctions of mini-organs in breast cancer patients, slightly different from coral corals.

With these detailed images, Florijn Dekkers can not only test the medicines used to treat cancer. You can see exactly how much blood vessels grow in the tumors formed by the duct channels in the breast tissue can even observe breast cancer tumor growth in experimental mice to find out which tumor cell line responds to therapy and which does not.

ETH's researcher helps

But what if you did not have to arrange the small organoids? What if larger, more mature structures were created in the lab? For this, Hans Clevers is working with EPFL's bioenergy and science researcher Matthias Lütolf. Lütolf combines the new biomass with microchips to simulate the three-dimensional structure of real organs as much as possible. "We want to monitor stem cell growth and organoid development," says Lütolf. Contrary to the laboratory, in the human body, not only growth factors play a role in the development of organs, but also the effects of adjacent tissues.

For example, in small channels of microchips, it can simulate the blood flow of the real organs. Contrary to the small shapes in Clever's lab, the smaller intestines produced by Lütolf are one centimeter long, tubular like the real bowel. Up to now, the bioengineer has only succeeded in breeding gut channels in mouse stem cells, but now also works with human cells.

Print the organs frame in 3-D

One day, says Clevers, bioengineers can print a kind of organ stand without cells in 3-D; With his colleagues, he places the correct organoids in the right places within the frame, for example in a lung, such as the alveoli, the trachea and the veins. Hans Clevers is only a matter of time before science is ready: "I think everything that nature has created can imitate it is never very complicated."

Internal physician Joan Nichols found an unusual organ stand, and in August he placed the Texas University of Texas researcher on the journal of Science Translational Medicine. He bought the dead porcine donor lungs, removed living cells, and left only the connective tissue racks. The stand was then colonized with the future lung owner of the future owner, another pig, and placed frames and cells in a bioreactor for 30 days. Then he transplanted the body.

Four pigs went through and microscopically small alveoli and a fine blood vessel network developed in each animal's body – this is an important precondition for gas exchange. "It would be interesting to colonize these lungs with organoids and blood vessel precursor cells," says Hans Clevers.

Laboratory skin

Sometimes, however, scaffolding is not necessary for the construction of the laboratory body. Italian and German researchers appeared around the plastic surgeon Tobias Hirsch last year in the journal Nature. A boy was transferred to the Bochum University Hospital, which grew up in the laboratory.

"A spectacular work," grateful Hans Cleverst, reminding him of the beginning of his organoid research. The first attempts at the time of skin rejuvenation at that time made him search for stem cells in the gut. This time, doctors successfully cover 80% of the patient's body surface, the boy suffered a serious hereditary disorder, his skin was mostly blistered, septicemia was dying.

But scientists are not just replacing dissolved skin. Gene therapy has also improved gene expression in the stem cells of the skin. Healthy skin grew up. It was a new work of art and gave a new life to the patient. (Editors Tamedia)

Created on 03.11.2018 at 9:01 pm


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