Synthetic tissues build and regenerate themselves.
Synthetic biology involves the fabrication of previously non-existent biological components and systems. Synthetic biology encompasses quickly manufacturing catalogued DNA sequences and assembling them into new genomes. A main goal of synthetic biology is the multistep production of natural products to one day enable organ regeneration and production. 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 simple organisms or the first stages of embryonic development. The team state 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 which grow with the right connections to the rest of the body. The study is published in the journal Science.
Previous studies show that a critical part of development is that, as biological structures form, cells communicate with one another and make coordinated decisions on how to structurally organize themselves. The current study mimics this process via a powerfully customizable synthetic signalling molecule called synNotch, which allowed the researchers to program cells to respond to specific communication signals with bespoke genetic programs.
The current study uses synNotch to engineer cells which respond to specific signals from neighbouring cells by producing Velcro-like adhesion molecules called cadherins as well as fluorescent marker proteins. Results show that just a few simple forms of collective cell communication were sufficient to cause ensembles of cells to change colour 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 building three-layered spheres or starting with a single group of cells which sorted themselves into two distinct groups before forming a layered sphere. They even engineered cells that formed the beginnings of polarity axes, which define the body plans of many multicellular organisms.
Data findings show that simple starter cells could be programmed to develop over time to form more complex structures, much like a single fertilized egg divides and differentiates to form different parts of the body and distinct tissues like skin, muscle, nerve, and bone. Results show these complex spheroids were also self-repairing; when the researchers cut the multi-layered spheroids in half the remaining cells quickly re-formed and reorganized themselves according to their intrinsic program.
The team surmise that they successfully programmed cells to enable spontaneous formation of multilayered structures, like those that form during embryonic development; the structures also showed regeneration after injury. For the future, the researchers hypothesize the self-organization of the elaborate structures which would eventually be needed for growing tissues for wound repair or transplant.
Source: UCSF Medical Center