Geometry helps scientists unlock mystery of human embryonic stem cell formation

In a breakthrough in stem cell research, scientists have developed a way for human embryonic stem cells to specialize, or form different cell types.

This differentiation has never before been successfully replicated with human stem cells in a laboratory. Previously researchers tried to induce stem cell differentiation with chemical applications. The successful research team used a combination of chemicals and, surprisingly, geometry, to achieve their results.

The Laboratory of Stem Cell Biology and Molecular Embryology at The Rockefeller University placed human embryonic stem cells in confined patterns on chemically treated glass. The chemicals induced micropattern formations, which researchers hypothesized, would trigger self-organization of the cells. They were right.

Upon further chemical application, gastrulation occurred and the cells differentiated into different germ layers, just as they would do naturally. Gastrulation is the process by which cells form endoderm, mesoderm and ectoderm, or specific cellular layers that eventually become the brain and skin, the muscles, and the blood, respectively.

The key to the whole process was the geometric confinement of the cells in the colony. The Rockefeller research team, led by Ali Brivanlou, was able to follow the pathways in the cells used to send signals that inhibit the cells in a colony from all developing the same way and forming the same germ layer. Other scientists involved in the study, published on June 29 in Nature Methods, include Aryeh Warmflash, Benoit Sorre and Eric Siggia of the Laboratory of Theoretical Condensed Matter Physics.

"Understanding what happens in this moment, when individual members of this mass of embryonic stem cells begin to specialize for the very first time and organize themselves into layers, will be a key to harnessing the promise of regenerative medicine. It brings us closer to the possibility of replacement organs grown in petri dishes and wounds that can be swiftly healed," says Brivanlou in a statement released by The Rockefeller University.

Scientists hoping to one day create engineered tissues for medical treatments should get excited, as per Warmflash. Confining the cells to specific geometries could be a very effective way to trigger cell specificity and, subsequently, tissue formation.

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