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ATLA - ISI
The Journal

 

Alternatives to Laboratory Animals - ATLA

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Cell and Tissue Engineering

 

cellsCells isolated directly from animal or human tissues often lack the ability to retain their functional and structural integrity when kept outside of the body for any period of time. Very often the cells simply stop growing or die.

 

There are a number of ways to make these cells survive, the most common of which is to introduce DNA that improves their longevity.

 

 

Recombinant DNA technology also allows the genetic make-up of particular cells to be altered (or engineered) to make them more suitable for assessing certain types of toxicity or to express targets for specific new drugs.

 

In many cases, these engineered cells are also modified so that they are suited to high-throughput screening. One way of doing this is to introduce a gene for an enzyme that catalyses the production of a coloured or luminescent (firefly) product. Examples include the beta-galactosidase gene found in some bacteria or luciferase gene found in some lower organisms that is responsible for their bioluminescence. Other genes code for fluorescent proteins such as green fluorescent protein from jelly fish.

 

However, in some ways these cells are overly simplistic and do not give information of direct relevance to human effects or safety. Part of the reason for this is the problems with differences in the way different people handle (absorb, metabolise, distribute and eliminate) a foreign substance.

 

More complex in vitro systems are based on growing two or more cell types together to mimic a biological system in co-culture or organotypic arrangements.

 

 

The best in vitro cell systems to use to predict human health effects of drugs and chemicals are those based on human cells, such as HepG2 liver cells, since species differences do not then have to be accounted for.