Artificial liver cells grown in mice



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Japanese researchers make a breakthrough in stem cell research
06.07.2013

Immense progress in the field of controversial stem cell research: Japanese researchers have succeeded in growing so-called “induced pluripotent stem cells” (iPS) human liver tissue, which after the transplantation into mice has partly taken on the role of a “natural” liver. The results of the scientists led by Takanori Takebe from Yokohama City University could have a significant impact on the development of donor organs - although it will probably take years before they are used in humans.

Researchers are breeding liver tissue from induced pluripotent stem cells As the scientists led by Takanori Takebe from Yokohama City University currently report in the journal "Nature", the study initially grew liver tissue from induced pluripotent stem cells (iPS), which was then transferred to a mouse and finally took over functions of a "natural" liver according to the article The findings of the Japanese researchers could represent a milestone in stem cell research - because "since the discovery of embryonic stem cells in 1981, none of the numerous laboratory studies has succeeded in developing such a complex vascularized organ as the liver from pluripotent stem cells," according to a recent one Press release from "Yokohama City University". With their study, the Japanese also made an enormous step for stem cell researcher James Adjaye from the University Clinic Düsseldorf: "This is a huge leap in the field," says Adjaye - and the method that the colleagues had used was "almost" too simple to be true. "

The first successes already after 48 hours. The Japanese had induced stem cells to mature into liver cells and connected them with human endothelial cells - which are necessary for lining the blood vessels - and precursor cells of the connective tissue, because only through the interaction of these three cell types can a liver in the embryo exist at all grow up. After various experiments, the researchers finally managed to create a four-millimeter-sized “organ bud” from this connection. The research team first transplanted the buds into the brain of mice in order to pass through an intracranial "window" - i.e. a thin glass pane that covers the hole in the skull - being able to observe the further development and made an astonishing discovery: "After 48 hours, the transplanted liver buds had already made contact with the vascular system of the mice," the researchers said in their article. Over the next few days, the liver cells matured and eventually took on specific functions - such as the production of proteins such as albium or the breakdown of medicines.

Artificial “mini liver” could be life-supporting for patients Nevertheless, the artificially produced mini liver is “far from a real liver”, as Stuart Forbes, transplant doctor from the University of Edinburgh adds, because among other things the liver from the petri dish would the bile ducts are absent - nevertheless the retort organ could theoretically at least partially take over the functions of the liver, so that "patients [.] might be kept alive until their liver has regenerated or a donor organ is available "Forbes says - that alone would be a major medical advance, because in Germany alone thousands of people are waiting for life-saving organ donation, but suitable organs are rare, especially because the willingness to donate is declining due to the fact that several organ donation scandals have become known to the population.

"Study offers a promising new approach in the field of regenerative medicine"
Accordingly, Takanori Takebe does not consider his work to be over - because "although efforts must be made to translate these techniques into therapeutic measures for patients, this proof of feasibility of organ bud transplantation offers a promising new approach in the field of regenerative medicine," said the research team in the magazine "Nature". Accordingly, in a further step, the attempt should be made to shrink the liver buds even more so that they can be injected directly from the Petri dish into the liver portal vein. The idea behind it: the blood could distribute the buds in the vascular system of the liver and immediately take on specific functions. While the first experiments with mice had already started, according to Takanori Takebe it would still take at least ten years before the first studies on humans can begin - which is also the case for Tobias Cantz from the Hannover Medical School and the Max Planck Institute for Molecular Biomedicine is realistic assessment.

There are still some problems to be solved for the first experiments on humans. According to Cantz, there are three basic problems that have to be dealt with first: On the one hand, the human liver would simply have a lot more weight than a mouse liver, so that “[…] larger or more liver Buds that still have the same properties ”would be needed. In addition, it must be ensured that the use of induced pluripotent stem cells does not pose any risk to the patient, and that a suitable location must be found where the mini-retort livers can be transplanted. Despite his objection, Tobias Cantz is also enthusiastic about the findings of his Japanese colleagues: “What is particularly fascinating is that the stem cells organize themselves and quasi form organ buds. So far, it has been assumed that this only occurs during embryonic development. "(Nr)

Image: Jörg Klemme, Hamburg / pixelio.de

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