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Stem cell therapies Prometheus unbound Researchers have yet to realise the old dream of regenerating organs But they are getting closer Jul 6th 2013 From the print edition Tweet PROMETHEUS a Titan bound to a rock by Zeus endured the daily torture of an eagle feasting on his liver only to have the organ regrow each night Compared with this spectacle a video on the website of Nature this week seems decidedly dull It shows a collection of pink dots consolidating into a darker central glob But something titanic is indeed happening The pink dots are stem cells and the video shows the development of a liver bud something which can go on to look and act like a liver Takanori Takebe and Hideki Taniguchi of Yokohama City University in Japan who made the video have created working human liver tissue In this section Prometheus unbound Beans talk A pile of wood The elephant in the room Reprints Related topics Technology Stem cell research Health and fitness Science and technology Medical technology Researchers have long dreamed that stem cells might be used to repair or replace damaged tissue an aspiration known as regenerative medicine Embryonic stem cells in particular are pluripotent meaning they are able to become any other type of cell And it is now possible to induce pluripotency in cells that have not come from embryos thus circumventing the ethical minefield previously associated with obtaining them Last year Shinya Yamanaka of Kyoto University won a Nobel prize for the invention of induced pluripotency He had shown how four signal proteins can reprogram adult cells into a pluripotent state Beside dealing with the ethical problems of embryonic cells Dr Yamanaka s induced pluripotent stem iPS cells allow at least in theory a treatment to be created from a patient s own body This would have his own genetic make up and would thus not attract the attention of his immune system Realising such treatments has been fiendishly difficult But Dr Takebe s paper in Nature is one of several signs that the Promethean dream is slowly coming to life Budding hope Clinical trials of pluripotent cells are already happening though they hark back to the days when only cells derived from embryos were available An American firm called Advanced Cell Technology ACT is using them to treat macular degeneration a cause of blindness Last year it reported promising results in two patients and Gary Rabin the firm s boss says tests continue Even if this specific approach works though it is likely to be overtaken by iPS technology The Japanese not surprisingly are in the lead Soon the country s health ministry is expected to approve the first clinical trial of iPS cells also for macular degeneration But ACT is not far behind It hopes to begin a trial of platelets blood cell fragments involved in clotting made from iPS cells And other firms want to treat everything from Parkinson s disease to glaucoma to multiple sclerosis Academia is pushing ahead as well Inspired by Dr Yamanaka s work people are looking for other shortcuts to pluripotency Marius Wernig of Stanford University for instance has worked out how to use three proteins to turn connective tissue cells into neurons Deepak Srivastava of the University of California San Francisco meanwhile has shown how to convert connective tissue into heart cells Other research is going beyond simple cell cultures In 2011 Yoshiki Sasai of the RIKEN Centre for Developmental Biology in Kobe showed how mouse embryonic stem cells if mixed with a few appropriate growth factors quickly form a three dimensional cluster made of the precursor cells to neurons This cluster then turns into something resembling the back of an eye Last year Dr Sasai repeated the trick with human cells The dream is to make a complex organ from scratch With this in mind researchers at Wake Forest University in North Carolina have used a three dimensional printer to produce an artificial kidney using immature kidney cells But if such organs are to work in people they will need blood vessels to deliver oxygen and nutrients The way to do that might paradoxically be for scientists to do less Instead of making the whole organ in a laboratory they might create a less developed form as Dr Sasai did with his proto retina and then leave the rest of the work to the body This is what Dr Takebe has done with his liver buds He coaxed some iPS cells into becoming liver endodermal cells The endoderm is one of the three cell layers of which the youngest sort of embryo is composed and is the layer from which the liver develops He then cultured them with two other cell types endothelial cells which make up the inner linings of blood vessels that were derived from umbilical cord and mesenchymal stem cells derived from bone marrow which can differentiate into several kinds of cells though not as many as pluripotent cells Cultures without mesenchymal stem cells failed to form a cluster Those without endothelial cells failed to create a network of blood vessels But together the three types of cell with little additional prodding formed a bud within two days At six days this bud was expressing genes known to be early markers of the liver And when Dr Takebe implanted such buds into the brains of mice whose immune systems had been disabled to prevent rejection he chose the brain because it is easy to fit the cranium with a tiny clear plate so that you can see what is going on he observed th

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