Engineered cells guide stem cells to form specific tissues

Engineered cells have been developed that can direct stem cells to form specific tissues and organoids, which may aid in the understanding and treatment of complex diseases.

Researchers from the University of California, San Francisco, and Cedars-Sinai, Los Angeles, California, have developed cells that deliver instructions to guide stem cell differentiation. Termed 'synthetic organiser cells', these cells were able to direct stem cells to form rudimentary organ-like structures, including brain and heart tissue. The study, conducted in mice, was published in Cell.

'By controlling and reshaping how stem cells differentiate and develop, it might allow us to grow better organs for transplantation or organoids for disease modelling and eventually utilise it to drive tissue regeneration in living patients,' said co-lead author Professor Wendell Lim from the University of California.

The synthetic organiser cells were genetically engineered to adhere to mouse embryonic stem cells by forming either a node on one side of the stem cell cluster or a shell surrounding them. They were then controlled by a chemical switch to turn the secretion of specific growth factors on and off. This technique means the growth factors form a concentration gradient across the stem cells which coaxes them to grow into specific complex tissues and organ-like structures. The researchers also included a switch to stop the synthetic organisers when needed.

Using the synthetic organiser cells, the researchers were able to more precisely direct stem cell growth and differentiation. In particular, the researchers were able to initiate the growth of a mouse body stretching from head to tail.

'By changing the placement of the [synthetic] organiser cells, and what signals they produced, we could finely tune how those signals spread through groups of stem cells,' said co-lead author Professor Ophir Klein from Cedars-Sinai. 'In one case, we saw a gene expression response resembling early growth of the entire body. In another case, we got a response resembling just one region of the body.'

Beating cells have been grown before in vitro (see BioNews 1195, 1102, and 1097). Yet, in a further experiment in which the synthetic organiser cells directed the development of a heart-like structure, Professor Lim explained that the beating chamber and early blood vessels that were formed is a step forward for synthetic development.

'The remarkable science of programming instructions to coax stem cells could one day open the door to tackle complex diseases,' said Professor Klein. 'We could generate specific cell types, like a beta cell to make insulin or a neuron to treat Parkinson's disease, within the context of a larger piece of tissue or even a whole organ. This work opens many new and exciting possibilities.'