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3D scaffold elevates drug screening results

By Dr Matt Wilkinson , 20-Sep-2007

UK researchers have developed a plastic cell scaffold that enables cells to be grown in realistic 3D structures and promises to enable better cell based drug screening results.

The new scaffold offers a cheap and straightforward way of cultivating cells in 3D, leading to more realistic structures that mimic how cells grow in the body better. This, in turn, leads to drug screening results that are more comparable to in vivo responses.

 

 

 

This latest research, published in the Journal of Anatomy was conducted at the University of Durham and the scaffold technology has been licensed to university spin-out ReInnervate.

 

 

 

The study showed that using the highly porous polystyrene scaffold to grow HepG2 liver cells led to cultures that gave more life like responses to the hepatotoxic anticancer drug methotrexate (MTX) than 2D cell cultures.

 

 

 

The scaffold, which is currently being commercialised by ReInnervate, will compete against other scaffolds, such as Invitrogen's macroporous alginate sponge scaffold AlgiMatrix .

 

 

 

"Industry wants cells that respond to a drug in the same way each time they are screened, this leads to more reliable results. What ReInnervate is all about is developing these enabling technologies to help other scientists by improving the tools they have available to them," said Dr Przyborski.

 

 

 

"Many drugs fail at the moment when they get into animal and human trials, if you can get more accurate in vitro assessment at an early stage using well-validated cell culture systems then the attrition of drugs will be less and the development costs reduced."

 

 

According to Dr Stefan Przyborski, lead author of the study and chief scientific officer at ReInnervate, the use of the polystyrene scaffold (the material from which most tissue culture flasks are made from) means that cell biologists only need to study how the cells respond in 3D rather than also needing to study how they respond to the AlgiMatrix.

 

 

"In total we've tested the growth of 8 different cell types on this scaffold, we've looked at stem cell differentiation, neurite outgrowth, neural development, liver cells, bone formation, fibroblasts and other basic cell types," said Dr Przyborski.

 

 

 

"We've now built up a wealth of information that shows that using the 3D scaffold you either get enhanced growth or function compared to growing the cells on a 2D platform."

 

 

According to Dr Przyborski, the technology in its simplest form is a well engineered piece of plastic.

 

 

 

"Our patent position revolves around being able to control the properties of the scaffold, such as the porosity, and that's really important as if you have a material that is too porous you won't enable cells to grow in 3D. If the voids are too small then cells won't be able to enter the material," he said.

 

 

 

"Another important factor is the thickness of the scaffold, and we've developed a way to engineer it into a very thin layer 150µm thick. This can then be placed in the bottom of any microplate or cell culture flask."

 

 

The scaffold to be used with a whole range of cell culture systems currently in use so that customers will not need to change their existing screening set ups.

 

 

 

"In our research labs we're currently looking at ways to make the plastic clever by coupling molecules that encourage stem cells to differentiate in a specific way to its surface," said Dr Przyborski.

 

 

 

One possible drawback of the system is that the scaffold is not optically clear, making imaging of the cells inside the scaffold difficult. Dr Przyborski said that confocal imaging could overcome this problem or that researchers could embed the scaffold in resin before sectioning it to enable more conventional imaging to be conducted.

 

 

 

Another use for the scaffold that the researchers are looking at is the use of the scaffold in 'cell factories' for bioprocessing applications. This would be achieved by grinding up the scaffold into beads before growing the cells in a large vessel and Dr Przyborski said his group had just finished a pilot study into this application.

 

 

 

The company is currently talking to potential licensees and are trying to either license the technology or secure a supply deal and are trying to raise capital to support the initiatives within the company.

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