Geometry Allows Stem Cells To Organize, Differentiate Naturally

Rockefeller University

While researchers have been able to push human embryonic stem cells (hESCs) into differentiating into specific tissues by exposing them to various growth factors, they have previously been unable to replicate the formation of germ layers that occurs early in embryonic development. However, a team from from Rockefeller University has found the solution lies in the physical arrangement of the cells, not just from chemical signaling. The team was led by Ali Brivanlou and the paper was published in Nature Methods.

"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," Brivanlou said in a press release. "It brings us closer to the possibility of replacement organs grown in petri dishes and wounds that can be swiftly healed.”

Around one week after conception, the little round ball of hESCs begins to specialize and differentiate into three germ layers, the endoderm, mesoderm, and ectoderm. These layers will go on to develop the 200 different types of cells in the fully developed human body.

The team altered the geometry of the growing hESCs by etching small circular micropatterns into class that held the cells in a certain position. When BMP4, a growth factor, was applied to the restricted cells, they began to develop the distinct germ layers just as they would have done in the uterus. Trials with hESCs that were not confined to a certain shape did not create those layers.

Additionally, the team was able to monitor the chemical signals the cells sent and received during the process of gastrulation for the first time. Understanding what factors makes these cells develop the way they do is an incredibly important insight into the basis of human development.

"At the fundamental level, what we have developed is a new model to explore how human embryonic stem cells first differentiate into separate populations with a very reproducible spatial order just as in an embryo," says lead author Aryeh Warmflash. "We can now follow individual cells in real time in order to find out what makes them specialize, and we can begin to ask questions about the underlying genetics of this process.”

While current work with stem cells typically relies on one type of cell, understanding the role of cellular geometry and knowing which chemical factors inhibit or promote expression of certain genes could eventually be used to create tissues made from multiple cell types; a huge biomedical advance.

"These cells have a powerful intrinsic tendency to form patterns as they develop," Warmflash continued. "Varying the geometry of the colonies may turn out to be an important tool that can be used to guide stem cells to form specific cell types or tissues."

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