Organelles

History

2024

The first testicular organoids were created. They will help treat infertility

On February 19, 2024, Israeli researchers at Bar-Ilan University reported the creation of the first testicular organoids. The achievement is expected to help to study in more detail the causes of male infertility, which, ultimately, may lead to the emergence of more effective ways to treat this disease.

Testicular organoids are grown from neonatal mouse cells. They mimic true testes, providing scientists with an effective model to analyze disorders of sexual development and infertility. It is noted that the dysfunctional development of the testicles can provoke a mixed manifestation of male and female sexual signs.

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The mice used as part of the work were genetically modified, allowing the researchers to monitor the presence and condition of Sertoli cells -- somatic cells located in the convoluted tubules of the testicles. They produce the hormone inhibin, which inhibits spermatogonium proliferation and enhances testosterone synthesis and sperm maturation from spermatogonium. 21 days after the growth began, the researchers obtained organoids containing all the major testicular cell types, including Sertoli cells. Although the organoids did not produce sperm, there were signs that this was possible.

The close similarity of organoids to true testes means they can be used to improve understanding of the mechanisms involved in sex determination and to find solutions to male infertility. In addition, testicular organoids derived from human cells can, for example, help young people who have undergone cancer therapy at an early age: such treatment can impair the ability of testicles to produce functional sperm. The proposed method involves collecting immature sperm, which are frozen and later used to create a fertile organoid that produces sperm.^[1]

Siberian scientists have grown "mini-brains"

Scientists at the ICG SB RAS have grown "mini-brains" - cerebral 3D organoids, three-dimensional tissues, similar in structure to certain parts of real organs. The press service of the institute announced this on February 7, 2024.

The synthesis occurred as part of a study of regions of the genome that probably played a key role in the evolution of the human brain. The study was sponsored by the Russian Science Foundation.

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As part of the study, scientists studied mutations in the contactin-6 gene (CNTN6) to improve understanding of human neurogenesis and the mechanisms of intellectual disability. Early studies have shown that the CNTN6 gene begins to work in the earliest stages of neurogenesis, and the degree of mutation of the gene greatly affects the severity of the pathology.

The fact that large mutations lead to dramatic consequences prompted us to think that inside the gene there may be functionally significant elements of the genome that affect the course of neurogenesis and on the study of which we need to focus, "said Tatyana Schneider, project manager, junior researcher at the Institute of Research and Development of the SB RAS.

The attention of scientists was attracted by the so-called HAR-elements (human accelerated regions) - enhancers (elements of the genome that stimulate the activity of genes), which undergo great changes in humans throughout evolution. Scientists have born the hypothesis that HAR elements are one of the main elements of brain evolution. There are two such elements in the CNTN6 gene, which was investigated by scientists.

Within the framework of this project, scientists set themselves the goal of describing in more detail how the "shutdown" of HAR elements affects neurogenesis and can be included in the development of mental retardation. In addition, scientists can also simulate genetic diseases caused by mutations in the CNTN6 gene and study the pathological mechanisms of the development of these diseases.^[2]

2022

Method of growing mini-organs, including intestines, discovered

In early December 2022, researchers from Tokyo Medical and Dental University discovered that spheroids grown in suspension, when transferred to a bioreactor, turn into human intestinal organoids and differentiate into complex intestinal tissue during transplantation. Read more here.

First transplantation of organoid into human

On July 7, 2022, the research team of the Tokyo Medical and Dental University announced that it had managed to carry out the world's first clinical transplantation of a mini-organ to a patient with ulcerative colitis.

Ulcerative colitis (UC) causes inflammation and ulcers in the digestive tract. This disease can be debilitating and can sometimes lead to life-threatening complications. UC belongs to a group of diseases called inflammatory bowel disease (IBD). The number of patients is growing in Japan, and worldwide, according to estimates, is about 5 million people as of August 2022. The usual treatment is to suppress inflammation with medication, but in severe cases the entire colon can be removed.

First transplantation of organoid into human

The clinical study began by collecting the patient's healthy colon mucosa and culturing them for about one month to form spherical organoids about 0.1-0.2 mm in diameter. On 5 Jul 2022, a mini organ or organoid was transplanted into the colon of the same patient by colonoscopy. The patient recovered and was discharged on 6 Jul 2022.

In previous experiments in mouse models, the team of scientists confirmed that when cells were cultured in organoids and then transplanted, the mucous membrane was restored in about a month and the clinical course improved. While stem cells themselves were not transplanted because they could not be cultured outside the body.

{{quote 'If our first human study using organoid transplantation produces good results, we expect that the development of organoid medicine to treat intractable digestive tract diseases such as Crohn's disease will progress. We have embarked on the path of developing new treatments for intractable diseases, "said Vice President and Professor Emeritus of Tokyo Medical and Dental University Dr. Mamoru Watanabe.

Since the patient's own cells are used, the advantage is that rejection during transplantation does not occur. In addition, since colonoscopy is used for collection and transplantation, laparotomy is not necessary, and treatment can be carried out by a minimally invasive method. After such transplantation, medical examination will be carried out after 4 weeks and after 8 weeks. The patient will be monitored for a year to check safety and efficacy. Further organoid transplantation will be performed for eight patients.^[3]

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