Team Discovers Underlying Mechanisms of 3D Tissue Training



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If you want to build an organ for a transplant, you have to think in 3D. By using stem cells, scientists are now able to cultivate organ parts in the laboratory, but one is far from building a fully functional and functional three-dimensional organ.

For students in regenerative medicine and developmental biology, that is why it is very important to understand how cells fold and move to form organs and body tissues. A team from the Institute of Sciences of Medicine and Medical Sciences of Kyoto University has now gained a new understanding of how mechanically stressed cells create the spherical structure of the body. ;eye.

Publication in Progress of science, the team discovered that individual cells together form a primordial cut-shaped structure – an "optical cut", by detecting the mechanical forces resulting from the deformation of the entire tissue. "In the past, we have been able to make the optical cup by growing ES – embryonic stem cells." To form a sphere, the tissue had to first protrude from the primordial brain tissue and then invaginate at the same time. inside, "explains the first author, Satoru Okuda.

"But how individual cells felt and modulated themselves to form this form had not been clear."

The team has developed a computer simulation that calculates the formation of three-dimensional tissue structures. With the help of this knowledge and previous experimental data, they built a virtual precursor eye and were able to predict the physics at the base of the cells forming a sphere.




Researchers have developed a simulation that shows how cells act during the formation of the optical cup. The results were then validated in the laboratory. Credit: Kyoto University / Eiraku Lab

Their findings show that during the formation of optical wells, a pattern of cell differentiation – pushing the cells into the form of wells – is generated, causing spontaneous folding of a portion of the cells into the tissue. This force caused by the "automatic bending" propagates towards the limit region, where other cells detect the stress.

"The combination of tissue deformation and stress on the edge of the optic cup generates a hinge that pushes the flexion cells further," continues Okuda, "leading to the cup-shaped structure." The next step was to check this prediction with the help of ES cells. "

Using mouse ES cells in culture, the team applied mechanical stress to specific points and was happy to detect the calcium responses, mechanical responses, and shape changes that they had predicted in the simulations.

These discoveries reveal a new role of mechanical forces in organ shaping, which is crucial for the formation of complex tissues, even in a petri dish. The team will continue to explore these strengths and seek to advance the field of regenerative medicine.

"Although our research demonstrates the ability to control the shape of organs made in vitro – using appropriate mechanical stimulation based on prediction – current techniques are still limited," concludes lead scientist Mototsugu Eiraku.

"We hope to improve the predictive accuracy of our simulations and recreate more complex tissues and organs in the future."


Explore further:
Optogenetics causes structural changes in tissues

More information:
"Mechanical feedback triggered by stress in self-organized optic cup morphogenesis" Progress of science (2018). DOI: 10.1126 / sciadv.aau1354, http://advances.sciencemag.org/content/4/11/eaau1354

Journal reference:
Progress of science

Provided by:
Kyoto University

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