Although scientists have been able to grow parts of an organ in a lab using stem cells, it is very different from creating a fully formed and functioning organ. To construct an actual organ such as for transplant, scientists need to think in three dimension. In order to cultivate the 3D perspectives, students of regenerative medicines and developmental biology need to better understand how cells fold and move to form bodily tissues and organs. In a recent study, published in the journal Science Advances, group of researchers at Kyoto University, Japan have acquired new understanding into a type of cells undergoing mechanical strain that can create the spherical structure of the eye.
The researchers have discovered that individual cells combine to form a primordial cup-like structure in response to mechanical forces generated by the tissue deformation. The team call it ‘an optic cup’ which they have successfully developed in the past by growing embryonic stem cells or ES cells in the lab.
First author Satoru Okuda explained that to develop the sphere form, the tissue needs to first protrude from primordial tissue of the brain and then invaginate inside. But, it is still not clear how each cell sensed and regulated themselves to form the optic cup.
The researchers also developed a computational stimulation that measures the formation of 3D tissue structure. With the gained knowledge and previous experimental data, they have been able to build a virtual precursor-eye and determine the physics influencing the sphere-forming cells.
According to the researchers, formation of the optic cup creates a cell differentiation pattern that forces the cells into the cup shape, causing major parts of the cells to spontaneously bend into a tissue. The force generated by ‘self-bending’ spreads into the circumference region, where other cells sense the mechanical strain.
The combination of the strain on the surrounding cells and tissue deformation creates a hinge that further pushes the folding cells, resulting into the cup-like structure, Okuda said. The following step was to confirm the prediction utilizing actual ES cells.
With the help of cultured ES cells of mice, the mechanical strain was applied to the particular points where the research team detected calcium responses, mechanical feedback, and changes in shape of the cell which they had predicted in the simulations.
The results uncover a crucial role of the mechanical forces in developing the structure of the eye or other organs, which is important in developing complex tissue, even in the lab. The research team plans to continue their investigation on these forces that can enhance the field of regenerative medicine.