Super-pluripotent stem cells
Working under the leadership of Rudolf Jaenisch, researchers at the Whitehead Institute for Biomedical Research, part of the Massachusetts Institute of Technology, converted human induced pluripotent stem cells (iPSCs) and human embryonic stem cells (ESCs) into cells with an increased level of pluripotency. The results of their work are published in the preliminary on-line version of the Proceedings of the National Academy of Sciences in the article "Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs".
Due to the ability to transform into almost all types of cells of the body, embryonic stem cells and induced pluripotent stem cells attract great attention of specialists. Ethical and legal issues have made research work with human embryonic stem cells difficult, so most of the research is currently conducted using mouse cells. However, there are a number of important differences between mouse and human embryonic cells, so there is a high probability that the result obtained in working with mouse cells will not be able to be reproduced on human cells.
Researchers have already learned how to prevent differentiation of mouse embryonic and induced pluripotent stem cells using genetic modification. However, mouse and human cells do not have different expression profiles even of matching genes, and their growth and differentiation depend on different signaling mechanisms.
Because of these biological differences, researchers call mouse embryonic and induced pluripotent stem cells "naive", and more mature human cells "primed" (prepared) for differentiation.
The authors suggested that this state of human cells may be the result of manipulations used in the creation and storage of cell lines. To create embryonic stem cell lines, scientists isolate cells from a blastocyst (an early embryo consisting of 80-100 cells) and place them in an environment containing other cells that synthesize factors necessary to maintain viability and prevent stem cell differentiation.
To create induced pluripotent stem cells, scientists embed 3-4 genes into the genome of adult cells, ensuring their transformation into cells similar in properties to embryonic cells, which are also cultured in a specialized environment containing auxiliary cells. Mouse cells are treated according to a similar protocol, however, for some unknown reason, with a slightly different result.
To test the possibility of returning "naivety" to human embryonic and induced pluripotent stem cells, the researchers used existing lines of such cells, in the genomes of which two genes were embedded, traditionally used to create induced pluripotent stem cells. In addition, additional growth factors were added to the culture medium of modified cells. After about three weeks, the cells acquired all the qualities inherent in their mouse counterparts.
Random embedding of genes can stimulate or suppress the expression of neighboring genes, which can lead to malignancy or cell death. To avoid this, the authors screened hundreds of small molecules in search of compounds with effects similar to the action of embedded genes. As a result, they created a cocktail of four molecules that increase the pluripotency of human embryonic and induced pluripotent stem cells.
Despite this achievement, the authors emphasize that today very little is known about naive human embryonic stem cells. However, they are confident that these cells open up new opportunities for scientists to study the biological characteristics of embryonic cells and in the future will have a great impact on the development of methods for the clinical use of stem cells.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on ScienceDaily: Scientists Create Human Embryonic Stem Cells With Enhanced Pluripotency.
07.05.2010