A research team at the UK Centre for Mammalian Synthetic Biology has made first steps towards creating self-assembling synthetic tissues de novo.
Prof Jamie Davies, Dr Elise Cachat and Weijia Liu engineered human kidney cells to express synthetic controllers that they then used to prune cells in a layer creating a tissue-like structure.
In conventional forms of bioengineering, tissue-like patterns of cells are created using techniques such as 3-D printing. However, there would be great advantages to getting cells to self-assemble, in much the way they do in Nature.
In previous studies the team created a simple system where human cells, that do not naturally form a pattern, are engineered to express one of two different cell adhesion molecules (‘E’ and ‘P’) tagged with different colour fluorescent proteins (red and green). When mixed, the cells naturally partner up with cells expressing the same adhesion molecule type resulting in an animal coat-like pattern of red and green fluorescent patches.
In this study, the team went a step further and added in a so-called morphogenetic factor – one that induces a change in the behaviour of the ‘E’ cell, in this case triggering the cells to die (apoptosis) in the presence of a chemical (tamoxifen). This time the mix of cells form the ‘coat-like’ pattern in a monolayer as before, but on treatment with tamoxifen the ‘E’ cells selectively die leaving holes not unlike the small channels seen in the kidney.
This simple system demonstrates and validates the idea of coupling synthetic biological morphogenetic effectors to synthetic biological patterning devices. It opens the path to engineering more sophisticated structures and, perhaps eventually, tissues.
Publication (open access)
Cachat, E., Liu, W. and Davies, J.A. Synthetic self-patterning and morphogenesis in mammalian cells: a proof-of-concept step towards synthetic tissue development. Engineering Biology, 6 pp.
ISSN 2398-6182 Available online: 01 September 2017
Above: Reticulum-like holes created after selective apoptosis of cells
Top: Self patterning of red and green fluroescently labelled human cells
Images courtesy of Dr Elise Cachat