New medical paradigm: Growing human organs in animals

The ability to manipulate genetics cuts in a number of ways. This way may sound a little strange: Take a mouse; implant human liver cells in it; watch them grow into a mouse-sized but human liver. It’s more complicated than that, but it works. There are reasons to do this. A lot of tests for new drugs, say for liver diseases, are never going to start with human test subjects – but a mouse with a ‘human’ liver, or one that functions just like it with human liver cells – that’s appropriate. In fact, liver diseases – especially Hepatitis-C – are very difficult to set up for experiment. Liver cells don’t take to growing in a dish, and small animals (e.g. mice, rats) can’t get Hepatitis-C.

Of course, knowing that implanting organs is difficult (rejection, infection, etc.), how is it that a mouse liver could accept human liver cells? The research team from the Salk Institute for Biological Studies (USA) explains it this way:

The Salk team had previously generated a mouse with a partially “humanized” liver, but wanted to improve their method to achieve almost complete transformation. They use a special mouse that has liver problems of its own, but whose problems can be kept in check with a drug called NBTC. Taking away NBTC allows human hepatocytes to take hold and populate the mouse liver with human cells.

The team perfected this system so that nearly 95% of the liver cells are of human origin, but the important question was whether they would behave like a human livers. To test this, the researchers exposed the mice to Hepatitis B and Hepatitis C and found that, unlike normal mice, which are resistant to these viruses, the chimeric animals developed the disease.

More importantly, using pegylated interferon alpha 2a-the standard treatment for Hepatitis C-the researchers showed that the “humanized” liver inside the mouse responds just like a normal human liver. The team also tested additional experimental drugs and found that they too behaved as they did in humans.

[Source: EurekAlert]

This method of testing liver cells and function through the intermediary of a mouse may not extend to other organs, but even so this is a ‘logical’ yet extraordinary application. It may be part of a growing capability to use animals of many kinds (pigs certainly jump to mind) to develop human analogous tissues and organs. Incidentally, the word for this kind of ‘guinea pig’ (test animal) is chimeric, which is ironically a lot like chimerical.

Research Spectrum

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