Alan Freeman asked:
Why is it that most parts of your body can repair themselves after damage, but your heart does not seem to be able to?
Alan in Durham City UK
Chris - Thatís not strictly true that most things can repair if they're damaged. Some tissues can replace lost cells. So if you cut yourself or graze some skin, it will grow back. But if you have a more catastrophic injury, then without the scaffolding of tissue there to support the growth and new stem cells there to provide a supply of new cells then tissues and complicated organs cannot repair themselves. The key thing really is in the stem cells, and the heart does appear to respond very badly to injury. If you have interruption to the blood flow of the heart by blocking a coronary artery, consequently, the muscle thatís supplied by that blocked artery is starved of oxygen and it does die, and the heart does not heal by repairing and replacing the lost cells in a human. Instead, the heart heals by producing fibrous tissue and you get a scar. That of course can't contribute anything to the pumping ability of the heart and so it increases the risk of things like heart failure.
But not all animals are like that and in fact, researchers including Kazu Kikuchi who published a paper in Nature in January of this year, they found that zebra fish can regenerate almost a third of their heart if you cut away a third of the left ventricle, the main chamber of the heart, the equivalent of that in the zebra fish, then the zebra fish will regenerate a whole new heart, and they thought, ďWell, if we can work out what they're doing, perhaps we can work out how to make humans better.Ē
They then used a specific construct so that they could turn on a gene just in heart muscle cells that labelled those cells with a glowing green colour. They then injured the heart and watched to see what happened as the heart repaired. Their theory was, well if stem cells are coming out and repairing the damage and they're nothing to do with the muscle, then the heart will just make a new muscle, and they won't glow green. If the muscle cells themselves in the zebra fish heart are repairing the damage, then you get a glowing green heart. Thatís exactly what they saw.
So what this tells you is that in these fish, when you injure the heart tissue, unlike in a human, the muscle cells respond to the injury by doing whatís called dedifferentiating. They make themselves less specialised. They become more stem cell-like. They then divide lots and lots of times to make a big pool of cells that then go to the right places, wire themselves up and then turn back into muscle cells to repair the damage.
They have found some genes including one called GATA-4 which seems to be turned on to do this process and is also used when the heart is developing in an embryo in the first place and this suggests, if we can work out how to do this, it might be possible to trick human heart cells to do the same thing, and therefore, turn into stem cell-like cells in the heart thatís been injured and therefore repair a damaged area, not with a scar, but with healthy fresh muscle again.
Helen - Itís extraordinary what we can learn from other members of the animal kingdom that will hopefully help ourselves in some of the problems that us humans have to deal with.
Chris - Well, exactly and I think this shows you how useful having something like a little fish can be - because fish are very cheap, they're very easy to look at and these fish are transparent which means that you can grow lots of them in a little tiny dish and see exactly whatís going on inside them with simple microscopy. This then informs the biology of much more complicated organs like rats and mice, and ultimately, humans. So itís making a very, very simple model of a complicated problem, and just distilling out what the crux of it is so we can hopefully find some answers.