The time between conception and becoming a fetus is a busy one if you're a human embryonic stem cell (hESC). As the embryo develops, hESCs are allocated into three distinct types of tissue through an orderly sequence of events. Although it's easy to grow hESCs in a culture dish, it's been impossible to make them repeat this orderly process - until now.
Scientists from the Laboratory of Stem Cell Biology and Molecular Embryology at Rockefeller University are using principles from geometry to control the patterns through which hESCs develop.
The scientists tested how stem cell identity is affected by an array of geometries by creating molds made of Polydimethylsiloxane (PDMS), a silicone-based elastomer. The group controlled the diameters and depth of the molds by 3D printing them. To get the hESCs to stick to the printed material, the scientists coated the molds with proteins that were known to increase cell adhesion. Once the molds were ready, the cells were added and allowed to incubate.
In its first investigation, the group determined whether these 3D printed molds allowed precise control of the size and geometry of the colonies of cells formed by cultured hESCs. The investigators found that the growth of hESCs on the molds was evenly distributed, which could enable them to control colony formation.
The scientists then investigated the use of various factors that control which types of specialized cells the hESCs form. By adding these factors to the molds, the scientists were able to create colonies of different cell types within the molds. They found that the cells not only differentiated as expected but also grew in separate colonies. (This growth in separate colonies was enabled by the 3D printed molds previously tested.)
Combined, the results showed that it's not only possible to get stem cells to differentiate into specific cell types (which has been done before), but also to control where those cell types form. In an important sense, this recapitulates what happens early on in embryonic development. The scientists believe this technique for growing hESCs may produce more knowledge about how embryonic development normally proceeds - and possibly offer greater control over how hESCs differentiate.
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