Genetically Engineered Cells Command Natural Ones to Repair and Grow

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.

Using a kind of genetically modified “boss” cell, the UCSF team was able to get other groups of individual cells to self-organize into multi-layered structures. These structures are similar — and in some cases identical — to simple organisms like bacterium or the tissues in the very first stages of human embryonic development.

The key to the new technique, according to researchers, is a customizable synthetic signaling molecule called SynNotch, short for synthetic Notch receptor. The SynNotch cell acts as a kind of middle manager molecule and allows researchers (senior management) to program nearby organic cells (salaried workers) with specific sets of instructions.

For example, the researchers engineered several groups of neighboring cells to produce Velcro-like adhesion molecules called cadherins along with fluorescent marker proteins. By sending specific directions through the SynNotch cells, researchers convinced the other cells to change color and self-organize into multi-layered structures similar to simple organisms or, significantly, human tissue.

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 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.”

Reference

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