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Shape of tissues influences stem cell growth

Issue date: 9/25/08
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"The concavity of an edge, rather than its presence inside or outside a monolayer, determined the mechanical forces, and therefore the cell type, present at that edge," Ruiz said.

This was proven by plating the cells on a pad that has little micro needles which detect tiny changes in forces. The tension in the cells which directed the MSCs to the osteocyte linege could be removed with these devices.

Feeding the cells a small molecule that blocks cell tension should stop this process, and that is exactly what was observed. Adding this molecule stopped the MSCs from turning into the osteocytes, which instead became adipocytes.

Other research into cell biology has shown that genes expressed in the two-dimensional cell cultures is not the same as the genes expressed in three dimensions. So, the U. Penn. team created 3D cell structures and looked for the same cell-lineage patterning they had seen in the 2D cell culture.

Even in these 3D blocks of cells, the outside of the box would be osteocytes and the inside of the box would be adipocytes. This mimics what is seen in actually structures in the body. Cells in the body form a hollow bone structure, which is filled with fat cells.

The novel work by this team has enormous implications for the future of stem cell biology research, especially for regenerative medicine. This emerging medical field works on creating tissue-specific cells and structures that can aid in the regeneration of damaged tissues in the body.

This research could help define limits on what structures could actually be made. Also, it illuminates a new role for mechanical forces in cell lineage specification and how it contributes with chemical morphogens to create the tissues of the body. Future work in this research will look more directly at the possibility that geometric abnormalities contribute to diseases.

"[The] most interesting question that remains to be understood is how mechanical force is transduced to the chemical signals that bring about the gene expression changes required for differentiation," Ruiz said.
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