Reconstituting epithelial microtissues with programmed size, shape, composition, spatial heterogeneity and embedding ECM Credit: http://www.nature.com/nmeth/journal/vaop/ncurrent/images/nmeth.3553-F3.jpg
A technique to build organoids of human tissues using a process that turns human cells into a biological equivalent of LEGO bricks has been developed. These mini-tissues in a dish can be used to study how particular structural features of tissue affect normal growth or go awry in cancer. They could be used for therapeutic drug screening and to help teach researchers how to grow whole human organs.
Called DNA Programmed Assembly of Cells (DPAC), thousands of custom-designed organoids, eg models of human mammary glands containing several hundred cells each, can be built in a matter of hours. “We can take any cell type we want and program just where it goes. We can precisely control who’s talking to whom and who’s touching whom at the earliest stages. The cells then follow these initially programmed spatial cues to interact, move around, and develop into tissues over time,” said Zev Gartner, PhD
“One potential application,” Gartner said, “would be that within the next couple of years, we could be taking samples of different components of a cancer patient’s mammary gland and building a model of their tissue to use as a personalized drug screening platform. Another is to use the rules of tissue growth we learn with these models to one day grow complete organs.”
METHOD: Gartner’s team incubate cells with tiny snippets of ssDNA engineered to slip into the cells’ outer membranes, covering each cell like the hairs on a tennis ball. These DNA strands act both as a sort of molecular Velcro and as a bar code that specifies where each cell belongs within the organoid. When 2 cells incubated with complementary DNA strands come in contact, they stick fast. If the DNA sequences don’t match, the cells float on by. Cells can be incubated with several sets of DNA bar codes to specify multiple allowable partners.
To turn these cellular LEGOs into arrays of organoids for research, they lay down the cells in layers, with multiple sets of cells designed to stick to particular partners. Not only does this let them build up complex tissue components like the mammary gland, but also to experiment with specifically adding in a single cell with a known cancer mutation to different parts of the organoid to observe its effects.
To demonstrate the precision of the technique and its ability to generalize to many different human tissue types, the research team created several proof-of-principle organoid arrays mimicking human tissues such as branching vasculature and mammary glands.
In one experiment, the researchers created arrays of mammary epithelial cells and asked how adding one or more cells expressing low levels of the cancer gene RasG12V affected the cells around them. They found that normal cells grow faster when in an organoid with cells expressing RasG12V at low levels, but required more than one mutant cell to kick-start this abnormal growth. They also found that placing cells with low RasG12V expression at the end of a tube of normal cells allowed the mutant cells to branch and grow, drawing normal cells behind them like a bud at the tip of a growing tree branch.
Gartner’s group plans to use the technique to investigate what cellular or structural changes in mammary glands can lead to the breakdown of tissue architecture associated with tumors that metastasize. They also hope to use what they learn from simple models of different tissue types to ultimately build functional human tissues like lung and kidney and neural circuits using larger-scale techniques.
“Building functional models of the complex cellular networks such as those found in the brain is probably one of the highest challenges you could aspire to,” Todhunter said. “DPAC now makes a lofty goal like that seem achievable.” http://www.newswise.com/articles/dna-guided-3-d-printing-of-human-tissue-is-unveiled
Recent Comments