Regrow Your Own

HOW DOES IT HAPPEN?

In many cases, regeneration begins when the mature cells at the wound site reverts to an immature state. The clump of immature cells, known as a blastema, regrows the missing part, perhaps by tapping into the embryogenesis programme that first formed the animal.

The blastema seems to derive its instructions from the wound-site cells and does not take cues from surrounding tissue if it is transplanted. For example, if a blastema made from a salamander8217;s limb is transplanted elsewhere in its body, it will still grow into a limb.

Initiation of a blastema and the formation of the embryo are obviously separate biological programs, but 8220;the processes converge at some point,8221; says Jeremy Brockes, a leading regeneration researcher at University College London.

WHAT ABOUT HUMANS?

People of course, do not form blastemas and regrow limbs, but humans are not entirely lacking in regenerative powers either. There are reports that the tip of the finger has been regenerated if the cut was above the last joint. And liver does regrow. Even after 75 per cent has been removed in surgery, the liver regains its original mass in two to three weeks.

The capacity for regeneration exists in such a wide variety of species, researchers believe that it is unlikely to have evolved independently in each. The machinery for regeneration must be a basic part of animal genetic equipment, they say, but the genes have for some reason fallen into disuse in many species.

And where necessity exits, the regenerative powers still work. In case of the human liver, the reason could be 8220;the extensive and recurring injury that the liver was exposed to in evolution: rotten food, plant toxins, viruses,8221; says Markus Grompe, a liver expert at the Oregon Health and Science University.

WILL BLASTEMA WORK IN MAN?

The reason for thinking regeneration in humans comes from genes.

Last December, Mark Keating, a vice president at the Novartis Institutes for Biomedical Research in Cambridge, Massachussets, who studies regeneration in zebra fish, identified a gene which initiates blastema in zebra fish.

This gene, called FGF20, and another he has found, HSP60, also exist in humans, suggesting the genetic basis for regeneration may still be in place even though the body can no longer evoke it.

If these genes exist in humans, they might be goaded into action by a new drug. And once a blastema had been induced at a wound site, regeneration researchers suggest, it might regrow the missing limb or organ.

IS THE THEORY POPULAR?

Blastema is studied in few laboratories. It was not even on the agenda of the research planning meeting held last October by the California Institute of Regenerative Medicine, which was dominated by stem cell biologists.

One reason for this orphan status is that the model animals used by most biologists, like the roundworm, the fruitfly and the mouse, happen to be ones that do not regenerate. So for long, the genetics of regenerating animals, like the salamander, remained largely unknown.

BLASTEMA VS STEM CELL THERAPY

The blastema8217;s reliance on internal information contrasts with a principal assumption of stem cell therapy, that stem cells inserted into a damaged tissue will use local cues to behave appropriately and integrate into the surrounding tissue. Stem cell therapists assume that injected cells can replace missing tissue by chemical signals from nearby cells. That is the solution a human engineer might logically think of, Dr Brockes says, but evolution has chosen a different one.

Many proponents of regeneration, while conceding they have a great deal more to learn, believe stem cell therapy too may not be as close to clinical use as its advocates suggest. The basic biology of regeneration is not yet fully understood, but nor is that of stem cells. Indeed, it may be premature to start thinking about how to use stem cells therapeutically, says Dr Snbsp;nchez Alvarado, a Hughes Institute researcher who studies flatworm regeneration at the University of Utah. 8220;Translating a biological process you don8217;t understand into technology is like trying to translate hieroglyphs without a Rosetta Stone,8221; he says.

Dr Grompe, the expert on liver regeneration, says that getting stem cells to behave properly in a patient8217;s body 8220;is a very, very difficult problem.8221; With transplanted stem cells, the usual outcome is 8220;nonfunctional at best and cancerous at the worst, because the local environment is not able to modulate the behavior,8221; he says. 8220;I think that cell therapy of the nervous system will be extremely difficult because of that. So much for stem cells curing Alzheimer8217;s.8221;

THEN, THERE8217;S THE COST

Dr Keating believes that the expense of stem cell therapy is a major consideration. Developing cells for every patient would be very expensive. Switching on the regenerative process with drugs, should that prove possible, would be cheap by comparison. Regeneration and stem cell therapy are promising aspects of regenerative medicine but both are still at the research stage. 8220;I8217;m very bullish on regenerative medicine,8221; said Dr. Keating. 8220;It will be a revolution, but it will take time. It would be a mistake to oversell it and promise too much too early.8221;

8212; NICHOLAS WADE