Stem cells obtained by nuclear transfer cause immune rejection
Researchers at Stanford University, together with colleagues from the Massachusetts Institute of Technology, as well as scientific institutions in Germany and the UK, have found that genetic differences in mitochondria contained in eggs used in nuclear transfer technology can trigger a previously unknown mechanism of immune rejection in mice. These data indicate the existence of a risk of developing such complications in the case of the transfer of such therapeutic approaches to clinical practice.
Stem cell therapy has a huge potential in repairing damaged organs and curing various diseases. One of the promising directions is the use of pluripotent stem cells capable of differentiating into almost any cells of the body. One of the methods of obtaining such cells is the somatic cell nucleus transfer technology, which consists in isolating the nucleus of an adult cell and introducing it into an egg cell, from which its own nucleus is previously removed.
Theoretically, the nuclei isolated from the patient's skin cells can be used to produce personalized pluripotent stem cells. According to one of the leaders of the study, Dr. Sonja Schrepfer, one of the most attractive characteristics of somatic cell nucleus transfer technology has always been considered the genetic identity of the patient and the resulting cells, the nucleus of which contains the patient's DNA. In theory, this should eliminate the problem of immune rejection of pluripotent cells as a genetically alien material.
About 10 years ago, Professor Irving Weissman from Stanford University, who at that time headed the commission of the US National Academies on cells obtained by somatic cell nucleus transfer, suggested that the immune system of the recipient of such cells could react to the proteins of their mitochondria – organelles, which are the energy centers of the cell and have their own DNA. The reason for the potential problem is that the cells obtained by the nuclear transfer method contain the mitochondria of the donor egg, which have donor DNA foreign to the recipient's body.
However, most experts were of the opinion that the mitochondria inside the cell would not come into contact with the recipient's immune system and, accordingly, would not trigger an immune rejection reaction. Until recently, no one has tried to refute or prove these assumptions.
In order to dot the "i", the authors used cells obtained by transferring the nuclei of somatic cells of adult mice into non-nucleated egg cells of animals of a genetically different lineage. When transplanting the obtained cells to mice of the donor line, they were rejected by the immune system even despite minimal genetic differences consisting in two substitutions of single nucleotides of mitochondrial DNA. The authors believe that such a reaction may well develop in the human body.
A drawing from an article in Cell Stem Cell.
Despite the success of experiments with cells of various animals, scientists have not been able to apply the method of transferring somatic cell nuclei to human cells for a long time. The statement about the successful reproduction of the procedure on human cells, made last year by researchers from the Oregon Health and Science University, revived interest in using this method of nuclei in clinical practice. Despite the fact that currently specialists mainly pay attention to working with induced pluripotent stem cells (iPSCs) obtained by dedifferentiation from skin fibroblasts, there are a number of situations when the use of the somatic cell nuclei transfer method is more appropriate.
The authors believe that potential immune rejection is not an insurmountable obstacle to the introduction of pluripotent stem cells obtained using the somatic cell nuclei transfer method into clinical practice. Most likely, this problem can be easily solved with the help of existing immunosuppressive drugs. Moreover, it is possible to reduce the immunogenicity of the transplant material by using eggs from closely related donors, for example, a mother or sister. However, they also note that in any case, the introduction of this technology into clinical practice is a matter of the distant future.
Article by Tobias Deuse et al. SCNT-Derived ESCs with Mismatched Mitochondria Trigger an Immune Response in Allogeneic Hosts published in the journal Cell Stem Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Stanford University Medical Center:
Pluripotent cells created by nuclear transfer can prompt immune reaction, researchers find.
Portal "Eternal youth" http://vechnayamolodost.ru27.11.2014