MODERN offices may scorn the stuff, but paper has found a new use in the laboratory 鈥� as the basis for 3D models of tumours and damaged hearts.
Chemist and his colleagues at Harvard University reckon that the balls of cells they have grown at the centre of stacked paper could help us better understand how tumours and damaged hearts respond to drugs, and even to select therapies most suited to individuals.
鈥淭he balls of cells built on paper could help us understand how tumours respond to drugs鈥�
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Cells tend to be grown on flat plates in the lab, which isn鈥檛 representative of the 3D structure of cells in the body. 鈥淚t鈥檚 nothing like human tissue,鈥� says Whitesides. In our bodies, cells are exposed to natural concentration gradients: the further away they are from major blood vessels, the less oxygen and nutrients they get. But in 2D cell cultures, such gradients aren鈥檛 present. 鈥淲e need to move away from those boring flatlands that cell culture dishes represent,鈥� says cell biologist of University College Dublin, who was not involved in the research.
Although techniques for growing cells in 3D exist, many are time-consuming and far from perfect. For example, once the cells have grown, the cultures need to be sliced with a knife to be analysed. 鈥淣ot only does this kill some cells, it鈥檚 extremely difficult to do,鈥� Whitesides says. His group has now developed a cheap alternative.
The team start by squirting a gel containing their cells onto small sheets of sterile chromatography paper. The cells they used included human lung cancer cells, human fibroblasts, which make up connective tissue, and mouse immune cells. 鈥淚 tried everything I could get my hands on,鈥� says Whitesides.
The cells seeped through the paper 鈥渓ike coffee through a napkin鈥�, he says. When the researchers stacked up eight sheets of cell-infused paper and suspended them in an oxygen and nutrient-rich broth, they found that the cells grew into a ball (see diagram).
To analyse how these cells behaved, the researchers simply peeled off the layers one at a time and analysed them individually. It seemed that the outer cells closer to the medium were nourished while the cells on the inside showed signs of being starved, which is what you would expect to happen to a tumour inside the body (Proceedings of the National Academy of Sciences, ).
Whitesides says that such 3D cultures will help probe diseases where some tissue is oxygen or nutrient deprived. This would include cases where heart tissue becomes damaged after being deprived temporarily of oxygen due to a blockage in the blood supply. 鈥淲e don鈥檛 know if tissue dies because of a lack of oxygen or when oxygen levels are restored,鈥� says Whitesides.
Cultures grown on paper could also be used to test drugs to treat these conditions, which could be personalised. 鈥淲e could take cells from a patient, grow them and see how they鈥檇 respond to different drugs,鈥� he says. The group also points out that paper has the advantage of being widely available, abundant and cheap.
, chief cell biologist at the National Institutes of Health in Bethesda, Maryland, calls the approach 鈥渃lever鈥� and 鈥渋nnovative鈥�. But since Whitesides鈥檚 team only grew the cells for nine days, he questions if the layers would be as easy to pull apart 鈥渁fter they have formed organised tissues鈥�. Reynaud, however, is convinced by the technique: 鈥淚 will happily peel from now on.鈥�
