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Great progress thanks to the mini-body – ScienceDaily

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Multiple stem cells, different growth factors, four to six weeks of time – and of course a lot of experience is needed to create a scaled-down, but still real and functional copy of the cervix in the lab.

A new publication that has now appeared in the magazine Nature Protocols shows in detail how the process works. This is the responsibility of Dr. Sindril Chumduri, head of the research group at the Department of Microbiology at the Julius Maximilian University of Würzburg (JMU). Infectious and cancer biologist has long studied the physiological processes in the tissues of the cervix. She is particularly interested in the conditions under which cancer develops there.

“Until recently, science lacked a system that would well reflect the cellular, physiological, and functional properties of different cell types in the cervix,” Chumduri says. This, she said, makes it difficult to study normal physiology, disease and infectious processes.

Of the three-dimensional organelles she has developed, she said, “new opportunities are now opening up to study cervical biology, infections and cancer development.” New applications in personalized medicine, the search for new active substances, genome intervention, disease modeling: with the help of organelles, scientists could put it all into practice much easier than before.

The cervix performs many functions

The cervix is ​​a complex structure. One of its most important tasks is to ensure the passage of sperm into the uterine cavity so that fertilization of the egg can take place. On the other hand, it should protect the female reproductive tract from dangerous invaders such as fungi, viruses and bacteria, as well as from ascending infections. Also, in late pregnancy it should be able to expand significantly so that the fetus can pass through it.

Anatomically the cervix forms the connection between the uterine cavity and the vagina. It consists of the so-called endocervix, which is adjacent to the uterus, and the ectocervix, which protrudes into the vagina. They are lined with different cell types: while the endocervix has a columnar epithelium, the ectocervix has a multilayered squamous epithelium. Where these two areas merge, they form a transition zone and are particularly prone to infection and tissue formation. For example, most cervical cancers originate from there.

Stem cells as starting material

To develop 3D cervical organelles Sindrila Chumduri and her team chose adult stem epithelial cells as the starting material. They were taken in biopsies from both the endocervix and the ectocervix. With the help of unique combinations of growth factors as well as different cultivation methods, they were able to restore the natural three-dimensional architecture and composition of tissues, as well as the functional properties of the original tissue and preserve them for a long period of time.

In more advanced experiments, scientists have also genetically manipulated stem cells. “We implanted stem cells with the HPV human papilloma virus genes that are responsible for the development of cancer,” Chumduri says. This could potentially unravel a mystery that science has been working on for a long time.

Deadly comorbid infections

Although HPV is known to be the driving force behind most cervical cancers, virus infection is not synonymous with malignant tissue tumors: current statistics show that about 80 percent of all women experience HPV during their lifetime. However, only 1.6 percent of them have cervical cancer.

There are now suspicions that there are other factors that increase the risk of cervical cancer, such as co-infection with other sexually transmitted pathogens, such as a bacterial pathogen Chlamydia trachomatis. Genetically engineered human ectocervical organelles now allow Chumduri and her team to more closely examine the long-term effects of viral infection on the squamous epithelium of the cervix and the contribution of co-infections with other pathogens such as Chlamydia trachomatis.

Great potential for further progress

“Endocervical and ectocervical organelles are ideal, almost physiological three-dimensional epithelial tissues for the study and modeling of cervical biology, host-pathogen interactions and disease development,” she said. In addition, she says, they are ideal for studying the body’s response to antibiotic-resistant pathogens.

Organoids also allow us to study the response of the cervical epithelium to hormonal changes and their effect on stem cell regeneration, mucus production and innate protection against pathogenic microorganisms. Their long-term cultivation offers a unique opportunity to take a closer look at chronic or recurrent infections and their impact on host cells, she said.

In any case, Sindril Chumduri is convinced: “In general, the organelle model of the cervix offers great potential for further advances in the study of the biology of the female reproductive tract.”

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