CELLS that have been hailed as the future of transplant medicine could also
provide a quick, accurate way to identify drugs that might damage the liver. A
biotechnology company in California believes that cultures of embryonic stem
(ES) cells could screen out excessively toxic experimental pharmaceuticals
before they are tested on animals or people.
ES cells have the potential to develop into any of the body’s tissues. This
has led some researchers to suggest that they could be used to grow unlimited
supplies of tissues or organs for transplant
(“Supercell”, New Scientist, 24 April, p 32).
But VistaGen of San Carlos is more interested in the fact that they produce high
levels of enzymes that are normally found in the liver.
That’s important, because most drugs are metabolised in the liver, possibly
yielding toxic products. The liver is the organ most likely to be damaged by
experimental pharmaceuticals. “It’s the major clearing house for drugs in the
body,” says Ralph Snodgrass, a developmental biologist and chief executive
officer of VistaGen.
In an attempt to screen out dangerous compounds early on, pharmaceuticals
companies often test the effects of potential drugs on liver cells taken from
cadavers. But once in a Petri dish, human liver cells often stop producing the
enzymes that break down drugs into toxic by-products—so the side effects
of some drugs aren’t spotted until they show up in animal tests or even in
VistaGen’s scientists have treated mouse ES cells with two drugs known to
damage the liver, and several others with no known toxicity. The cells produced
a distinctive spectrum of proteins in response to the toxic drugs. Snodgrass
plans to repeat the experiment with human ES cells.
Frank Sistare, a pharmacologist with the Food and Drug Administration in
Washington DC, says that the VistaGen team must now prove that ES cells predict
drug toxicity better than current cell-culture systems.