16 May 2011

Horror story about induced pluripotent stem cells

Reprogrammed stem cells provoke an immune responseKirill Stasevich, Compulenta  

Induced stem cells, unlike embryonic ones, are attacked by the immune system and rejected by the body. This is due to the activation of genes, which happens when cells are reprogrammed – the protein products of these genes are not accepted by the immune system as "their own".

The results of research by molecular biologists from the University of California, San Diego (USA) call into question the rosy prospects for the use of induced stem cells in medicine. In an article published in the journal Nature (Zhao et al., Immunogenicity of induced pluripotent stem cells), scientists report that induced pluripotent stem cells cause immune rejection even when they are transplanted to a genetically identical animal.

The use of stem cells (SC) in medicine involves growing healthy tissue from them and transplanting it to replace the diseased or damaged one. Embryonic SCS differ from "adults" in that absolutely any tissue can be obtained from them. But the use of embryonic SC is associated with a number of problems, both technical and moral and ethical, so scientists have learned to obtain so-called pluripotent cells from ordinary adult cells. A mature human cell can be deprived of specialization and turned into an analogue of an embryonic stem cell. Thus, a person can replace, for example, a diseased fragment of the liver with a healthy one grown from his own skin cells, which were made pluripotent, and then sent along the "hepatic" path of development.

It turned out that everything is not so simple. A group of researchers led by Yang Xu transplanted genetically identical donor mice with various SCS, embryonic and induced. Embryonic SC during transplantation give birth to teratomas, tumor formations that are a hodgepodge of all cell types; teratomas are, as it were, a qualitative reaction to the ability of such cells to transform into any other type.

Teratoma with formed teeth and hair, cut from the ovaries of a 14-year-old girl
(photo by Terrortoma).

But induced SCS during transplantation to mice did not form teratomas, and if they did, then these neoplasms were attacked by the immune system and rejected by the body.

The researchers found that in teratomas created by induced SC, some genes are several times more active than in teratomas from conventional (embryonic) SC. Protein products of two such genes, Zg16 and Hormad1, are most susceptible to immune attacks. According to scientists, these genes are "silent" at the time of the formation of the immune system in the fetus, so the proteins they encode do not become "their own" for it. And reprogramming mature cells into embryo-like SCS can awaken these genes and provoke an immune response.

However, other scientists urge not to bury the hopes associated with the use of induced SC ahead of time. From the work of Yang Xu's group, it is not entirely clear what exactly the immune system reacts to: immature stem cells or already differentiated teratoma cells. Since in medicine it is supposed to transplant not the SCS themselves, but the tissues grown from them, the answer to this question seems very important. But even if the immune response is caused by mature, specialized cells, do not forget that these data were obtained in mice, and not in humans, where the picture may be completely different. Finally, the question remains which cells provoke the immune system, because it may be that the immune response is directed at epithelial cells, and not, say, nerve cells. The authors themselves say that they received induced SC in two different ways and observed differences in the intensity of rejection of the transplanted cells. In short, the results speak more about the need for further research than about the collapse of hopes placed on the UK and regenerative medicine.

Prepared based on the materials of Nature News: Reprogrammed cells trigger immune reactions in mice.

Portal "Eternal youth" http://vechnayamolodost.ru16.05.2011

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