Are induced pluripotent stem cells ready for use?

Since the end of 2007, after the publication of articles by the first two groups of researchers who achieved the transformation of skin cells into so-called induced pluripotent stem cells, the methods of reprogramming adult fibroblasts into cells that do not differ in properties from embryonic ones have been significantly improved. Perhaps the technique developed by a group of Korean and American researchers led by Kwang-Soo Kim from Harvard Medical School and Korean CHA University will be safe enough to use reprogrammed fibroblasts to treat people.

Last month, a group of researchers led by Sheng Ding from the Scripps Research Institute developed a safe technique for producing induced pluripotent cells based not on changing their DNA, but on the use of genetically modified proteins – factors that reprogram cells. All previous technologies were based on the introduction of genes or matrix RNAs encoding these proteins into cells, which is fraught with global changes in the genome of patients and cancer cell degeneration.

Modification of reprogrammer proteins by the Shen Ding method implied the production of recombinant proteins carrying additional "tails" of the amino acid arginine molecules at one end, which promotes the penetration of proteins into cells. These constructs were obtained using a plasmid DNA vector in E.coli culture and isolated in pure form. Recombinant proteins in combination with valproic acid, which in its pure form is used as a broad-spectrum antiepileptic agent, successfully reprogrammed mouse fibroblasts into pluripotent cells.

In an article by Kim D. et al. Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins, published in the latest issue of Cell Stem Cell, describes a very similar, but, according to the authors, even safer method of reprogramming cells. Its difference is that recombinant reprogrammer proteins were obtained not in bacteria, but in cultured human cells. Human fibroblasts were treated with an extract of purified proteins, after which they became pluripotent. This technique does not require the use of additional chemicals, as was done in the first study. The cells were successfully tested for pluripotency, and DNA analysis showed that the profile of genetic expression in these cells coincides with the expression profile of embryonic stem cells.

The authors of the latest study believe that the effectiveness of their method is higher than in the previous case, since proteins obtained in cultured human cells are more "physiological" than proteins obtained in bacterial culture. In addition, the authors emphasize that no additional drugs are required, although Shen Ding claims that the valproic acid he used does not have a negative effect on cells.

The proposed technique does not imply any temporary or permanent changes in the cell genome, and therefore does not require significant refinement and modification. The joint American-Korean enterprise Stem Cell & Regenerative Medicine International, created six months ago by one of the leading companies in the field of stem cells, Massachusetts Advanced Cell Technology, and Seoul firm CHA Biotech, plans to submit an application to the FDA in the second half of 2010 to conduct clinical trials of a new method. Before that, scientists will have to check whether the use of pluripotent cells induced by the described method does not have long-term negative consequences, and also study the possibilities of differentiation of such cells, for example, into hematopoietic cells, which could be used in the treatment of diseases of the hematopoietic system and blood vessels.

Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Patient-ready iPS cells?01.06.2009