Artificial liver cells bred in mice

Japanese researchers make breakthrough in stem cell research

06/07/2013

Immense progress in the field of controversial stem cell research: Japanese researchers have succeeded, so-called „induced pluripotent stem cells“ (iPS) to grow human liver tissue, which after the transplantation into mice partially the tasks of a „natural“ Liver has taken over. The findings of scientists led by Takanori Takebe of Yokohama City University could significantly influence the development of donor organs - although it will take years to become operational in humans.

Researchers breed liver tissue from induced pluripotent stem cells
As the scientists around Takanori Takebe from the Yokohama City University currently in the journal „Nature“ In the course of the study, liver tissue was initially grown from induced pluripotent stem cells (iPS), which was then transferred to a mouse „natural“ Liver. 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“, such a current press release of „Yokohama City University“. For the stem cell researcher James Adjaye from the University Hospital Düsseldorf, the Japanese have made an enormous step with their study: „It's a giant leap in the field, "says Adjaye, adding that the method their colleagues used was the method „almost too simple to be true. "

First successes already after 48 hours
For example, the Japanese had induced stem cells to mature into liver cells and linked them to human endothelial cells - which are necessary for the lining of the blood vessels - and precursors of the connective tissue, because only through the interplay of these three cell types can a liver ever grow into the embryo. After several attempts, the researchers had finally managed to get out of this compound a four-millimeter-sized so-called „organ bud“ emerged. The research team now transplanted the buds first into the brain of mice, through an intracranial „window“ - i.e. a thin sheet of glass that covers the hole in the skull - to be able to observe the further development and made an amazing discovery: Because already „After 48 hours, the transplanted liver buds had contacted the vascular system of the mice“, the researchers in their article. Over the next few days, the liver cells matured and finally took over the researchers' specific functions - such as the production of proteins such as albumen or the breakdown of drugs.

artificial „Mini-liver“ could be life-sustaining for patients
Nevertheless, the artificially produced Minileber „far from a true liver, "adds Stuart Forbes, a transplant physician at the University of Edinburgh, because the liver from the Petri dish would lack the bile ducts, but the retort organ could theoretically at least partially bypass the functions of the liver Forbes said that "patients might be kept alive until their livers have regenerated or a donor organ is available," Forbes said. That alone would be a major medical advance, waiting alone in Germany Thousands of people on a life-saving organ donation, but matching organs are rare, especially because the willingness to donate due to the discovery of several organ donation scandals in the population goes back.

„Study offers a promising new approach in the field of regenerative medicine“
Accordingly, Takanori Takebe does not consider his work to be over for a long time - because „Although efforts must be made to translate these techniques into therapeutic measures for patients, this proof of concept of organ graft transplantation offers a promising new approach to regenerative medicine“, according to the research team in the magazine „Nature“. Accordingly, in a further step, the attempt should be made to reduce the liver buds even more to be able to inject them directly from the Petri dish into the Leberpfortader can. The idea behind it: About the blood, the buds could spread in the vascular system of the liver and soon take on specific functions. While initial experiments with mice have already started, Takanori Takebe believes that it would take at least another ten years for people to begin their first studies - including Tobias Cantz of the Hannover Medical School and the Max Planck Institute for Molecular Biomedicine realistic assessment is.

For the first experiments on humans still some problems must be solved
Because, according to Cantz, there are three fundamental problems that need to be addressed first: First, the human liver would simply spend much more weight than a mouse liver, so „[...] larger or more liver buds that still have the same characteristics“ would be needed. In addition, it must be ensured that the use of induced pluripotent stem cells poses no risk to the patient and, moreover, that a suitable place should be found where the mini-retort livers could be transplanted. Despite his objection, Tobias Cantz is also enthusiastic about the findings of his Japanese colleagues: „Above all, it is fascinating that the stem cells autonomously organize and virtually form organ buds. So far it has been assumed that this occurs only during embryonic development. "(Nr)