A breakthrough method of turning adult cells into induced pluripotent stem cells, i.e. cells with the properties of embryonic ones, has been found. The method might well change the stem cell research landscape, as using of embryos as a stem cell source may turn unnecessary. The researchers from Harvard Stem Cell Institute, the authors of the method, reported their finding in the journal Cell Stem Cell.
The history of performing this type of reprogramming reaches back 2006, when a Japanese scientist Shinya Yamanaka produced cells having embryonic stem cells properties out of adult skin cells, namely, fibroblasts. He called these cells iPS cells because they could be turned into any cell type of the body.
To enable such a transformation, Shinya Yamanaka used four genes to modify adult cells DNA. As these genes were inserted into genome of adult cells with the aid of viruses, applying iPS cells for diseases treatment bore at least two risks, such as risk of cancer development due to their integration into genome and the risk that the properties of the iPS cells would change unpredictably.
After that finding, scientists have been seeking other ways of converting adult cells into iPS cells, as it would enable developing treatment methods with the use of pateint's own cells and studying diseases more profoundly. It seems now that such a promising method has been found.
The new method does not involve integrating new genes into DNA of the cells subject to modification. Thus, the integrity of the initial genome is not affected, which means no risk of cancer. Moreover, it is by far more productive in quantitative terms, as it allows for increasing the conversion rate (the share of the starting cells transformed into iPS cells) from 0.001%–0.01% to 1%-4%. This may prove being very important in cases when a very small number of cells for modification could be got from the patient. Finally, iPS cells could be programmed to develop into specific cell types which could be used in clinical practice.
The core of the method is using synthetic ribonucleic acid (mRNA) instead of viruses for cells re-programming, as RNA cannot integrate into cell's genome and break genetic integrity of the cell. This artificial mRNA encodes production of biologically active substances that guide cell re-programming. Produced in this transformation cells resemble embryonic stem cells much more compared to cells re-programmed with the use of viruses.
Similarly, the RNA was used for further transformation of received iPS cells into target cells. To guide iPS cell differentiation into muscle cells, another artificial mRNA was created. The experiment succeeded.
During the research, the scientists have also found ways to get over natural cellular immune response associated with the insertion of exogenous RNA. Usually, introduction of exogenous RNA into the cell provokes anti-viral immune response which ends in a cell 'suicide'. In order to overcome that, the researchers modified mRNA so that it would not provoke immune response.