Synthetic tissues build and regenerate themselves.

Synthetic biology involves the fabrication of previously non-existent biological components and systems, consisting of quickly manufactured DNA sequences assembled into new genomes.  The main goal of synthetic biology is the development of multistep production of natural products to enable organ regeneration and production in the future.  Now, a study from researchers at UCSF demonstrates the ability to program groups of individual cells to self-organize into multi-layered structures reminiscent of the first stages of embryonic development.  The team states they hope their work will help guide the global medical community towards being able to program stem cells to repair damaged tissue, or even build new organs with the capacity to establish the right connections with the rest of the body.  The study is published in the journal Science.

Previous studies have shown a critical part of development is the formation of biological structures able to communicate with one another to make coordinated decisions on how to structurally organize themselves.   The current study mimics this process via a powerfully customizable synthetic signaling molecule called synNotch with the ability to program cells to respond to specific communication signals with bespoke genetic programs.

The current study uses synNotch to engineer cells with the ability to respond to specific signals from neighboring cells by producing Velcro-like adhesion molecules called cadherins as well as fluorescent marker proteins. Results show just a few simple forms of collective cell communication were sufficient to cause ensembles of cells to change color and self-organize into multi-layered structures akin to simple organisms or developing tissues.  The lab went on to program groups of cells to self-assemble in increasingly complex ways, such as three-layered spheres. They even engineered cells forming the beginnings of polarity axes, defining the body plans of many multicellular organisms.

Data findings show simple starter cells were programmed to develop into more complex structures, much like a single fertilized egg dividing and differentiating to form different parts of the body and distinct tissue types.  Results show these complex spheroids were also self-repairing when damaged, with the remaining cells quickly re-forming and reorganizing themselves according to their intrinsic program.

The team surmises they successfully programmed self-healing cells to assemble into multilayered structures, as seen in early embryonic development.  For the future, the researchers hypothesize the self-organization of the elaborate structures may eventually have applications in tissue engineering.

Source: UCSF Medical Center

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