Genetically Engineered Cells Command Natural Ones to Repair and Grow

The engineered cells mobilize adjacent, natural cells into complex structures.

Researchers programmed cells to self-assemble into complex structures such as this one with three differently colored layers. | Wendell Lim/UCSF
Researchers programmed cells to self-assemble into complex structures such as this one with three differently colored layers. | Wendell Lim/UCSF

The field of developmental biology is dedicated to one of the fundamental wonders of the universe: How do complex biological structures — brains, arms, people — emerge from a single fertilized egg?

It's a puzzler, all right. But new research out of the University of California, San Francisco suggests that we may have just cracked the first part of the complex code that informs embryonic development.

The research team used genetic engineering to program cells with simple rules that allow them to self-organize into multi-layered structures, similar to how birds form flocks or fish form schools. These structures are similar to tissues in the very first stages of human embryonic development.

The key to the new technique, according to researchers, is a customizable signaling molecule called SynNotch, short for synthetic Notch receptor. The SynNotch cells are programmed to respond in specific ways to the presence of adjacent cells.

For example, the researchers could engineer several groups of neighboring cells with SynNotch proteins encoding simple rules. When the engineered cells encounter one another, the rules trigger them to produce fluorescent marker proteins, as well as Velcro-like adhesion molecules called cadherins. The cells then start to stick together, leading to the formation of multi-layered structures similar to simple organisms or, significantly, human tissue.

In other words, the SynNotch programs allow the cells to organize themselves through spontaneous cooperation. The process is similar to how people might sequence themselves in a line by order of height. Without anyone in charge, the cells just keep shuffling around until the proper structure is achieved.

The new research was published in the journal Science.

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One of the potential applications of the technology is a very big deal. In fact, it's a kind of Holy Grail for developmental biology: The ability to grow entire replacement organs or limbs for wound repair or transplant.

According to the study's senior author Wendell Lim, chair of the department of cellular and molecular pharmacology at UCSF, the SynNotch technique is fundamentally different from other current tissue-generation techniques.

"People talk about 3D-printing organs, but that is really quite different from how biology builds tissues,” Lim said in a statement issued with the new research. “Imagine if you had to build a human by meticulously placing every cell just where it needs to be and gluing it in place. It's equally hard to imagine how you would print a complete organ, then make sure it was hooked up properly to the bloodstream and the rest of the body.”

If biologists can figure out a way to program increasingly complex structures, then natural cellular development would handle all the heavy lifting. Scientists would be, in effect, simply supplying the blueprints.

“The beauty of self-organizing systems is that they are autonomous and compactly encoded,” Lim said. “You put in one or a few cells, and they grow and organize, taking care of the microscopic details themselves."

One interesting note: Even though the SynNotch technique is in its very early stages, the research team was able to engineer some surprisingly complex and important structures.

For instance, they were able to generate cells that formed the beginnings of what is called “polarity” in biological systems. These are the distinct front-back, left-right, head-toe axes that define the body plans of organisms — humans included.

By deploying different types of cadherin adhesion molecules, the research team was able to convince cellular assemblages to divide into "head" and "tail" sections, or to produce four distinct radial "arms."

Insert your own Frankenstein joke here.