Cure hereditary diseases with stem cells?

Stem cells to cure a hereditary metabolic disease

10/13/2011

British researchers have produced so-called induced pluripotent stem cells (iPS cells) from skin cells of patients with metabolic disease and subsequently successfully transformed them into healthy liver cells. The healthy cells then tested the researchers in animal studies on mice, the hereditary disease „Alpha-1 antitrypsin deficiency“ to heal.

This is another step in the path to medical use of iPSCs, although the technique has so far only been tested on mice, write Allan Bradley and colleagues from the Sanger Institute in Hinxton, UK, in the current issue of the journal „Nature“. Genetic changes, which in previous experiments had led to the stem cells from developing cancer cells, have not occurred in the current experiments, the British scientists continue. Since the iPS cells are ethically and morally much less controversial than so-called embryonic stem cells, research raises great hope for the medical use of artificially produced induced pluripotent stem cells.

Healed liver disease with induced pluripotent stem cells
The scientists at the Sanger Institute, a not-for-profit genome research center in Hinxton nine miles south of Cambridge, are working to develop the „focused on genetic foundations of health and disease“, have achieved significant success in the development of induced pluripotent stem cells. In July, scientists from the Hannover Medical School (MHH) and the Max Planck Institute for Molecular Biomedicine in Münster reported on the successful use of iPS cells to treat liver disease in mice, and the British researchers have now confirmed these results. Allan Bradley and colleagues prepared iPS cells from skin cells from patients with a metabolic disorder, corrected the genetic errors that caused hereditary disease using two known techniques, and subsequently implanted the cells in mice suffering from the same metabolic disease. In this way succeeded the hereditary disease „Alpha-1 antitrypsin deficiency“ healing in the mice is reported by Allan Bradley and his team.

Alpha-1 antitrypsin deficiency
„Alpha-1 antitrypsin deficiency“ is a hereditary disease that, as a so-called monogenic disease, leads to severe impairment of the metabolism. The disease is caused by the mutation of a single gene, where the onset of the disease requires changes in both copies of the gene in question in the chromosomes of a patient. As Allan Bradley and colleagues report, about one in every 2,000 people of Northern European descent get sick „Alpha-1 antitrypsin deficiency“. The consequences of hereditary metabolic disease can range to liver cirrhosis, which in the worst case, a liver transplant is required, the statement of the British researchers. Bradley and his team are using a so-called transposon gene and special enzymes, the zinc finger nucleases, to remedy the genetic defects in iPS cells derived from the skin cells of three metabolic disease patients. Subsequently, the researchers used the human cells in the liver tissue of mice with the same metabolic disease. There, the iPS cells took over the function of the defective liver cells and thus helped to rid the mice of their genetic disease, write the British scientists in the journal „Nature“. Apparently, the human cells integrated relatively smoothly into the liver tissue of the mice. In contrast to earlier studies, no tumor cells were formed from the current iPS cell treatment, the researchers emphasized, adding that the method could therefore be used to treat monogenic diseases in the future. However, further studies are needed to further analyze the mutations in the genome of the iPS cells that occurred during the study, even if no tumor cells have developed from them, Bradley and colleagues said.

Criticism of stem cell research
The induced pluripotent stem cells have been explored as a possible replacement for the highly controversial embryonic stem cells for years, with the reprogramming of stem cells from other cells as an ethically acceptable alternative to embryonic stem cells. Moral and ethical concerns have deplored embryonic stem cells and have often been a source of criticism. For the production of the cells must be destroyed early human embryos. Last but not least, the breeding of embryos in the laboratory (cloning) for the production of stem cells, which was advocated by supporters of embryonic stem cells, triggered massive public protests. In Germany, the dispute between opponents and supporters of embryonic stem cell research also revolves around when an embryo under Art. 1 of the Basic Law is to be protected as a human life. Comparable ethical discussions are of secondary importance for iPS cells, but in the course of this year a controversy about possible health impairments caused by the pluripotent stem cells (embryonic and induced) has broken out. US scientists from the University of California, the San Diego School of Medicine and the Scripps Research Institute have identified severe genetic alterations in pluripotent stem cell lines that, in the worst case scenario, can lead to the formation of tumors. (Fp)

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Picture: Picture credits: Martin Gapa