HUMAN EMBRYONIC STEM CELLS. PROBLEMS AND PERSPECTIVES
N. N. Nikolsky,1 I. A. Gabay, N. V. Somova
Institute of Cytology RAS, St. Petersburg;
1 e-mail: Nikolsky@mail.cytspb.rssi.ru
Establishment of human embryonic stem cell lines is one the major achievements in the biological science in the
XX century and has excited a wide scientific and social response as embryonic stem cells can be regarded in future
as unlimited source of transplantation materials for the replacement cell therapy. To date human embryonic cell
lines are obtained in more than 20 countries. In our country the embryonic stem cell researches are carried out in
the Institute of Cytology RAS and the Institute of Gene Biology RAS. ESC lines are derived from placed in culture
inner cell mass of human preimplantation blastocysts used in the in vitro fertilization procedure. Studies with
human ESC go in several directions. Much attention is paid to the elaboration of the optimal conditions for ESC
cultivation, mainly to the development of cultivation methods excluding animal feeder cells and other components of
animal origin. Another direction is a scale analysis of gene expression specific for the embryonic state of the cells
and corresponding signaling pathways. Many efforts are concentrated to find conditions for the directed
differentiation of ESC into different tissue-specific cells. It has been shown that ESC are able to differentiate
in vitro practically into any somatic cells. Some works are initiated to develop methods for the "therapeutic
cloning", that is transfer and reactivation of somatic nuclei into enucleated oocytes or embryonic stem cell
cytoblasts. Of great importance is human ESC line standardization. However, the standard requirements for the cells
projected for research or therapeutic purposes may be different. It has been found that many permanent human ESC lines
undergo genetic and epigenetic changes and, therefore, the cell line genetic stability should be periodically
verified. The main aim of the review presented is a detailed consideration of the works analyzing the genetic
stability of human and mouse ESC lines. Human ESC lines established in our and as well as in other countries couldn't
be used so far in clinical practice. It is highly probable that undifferentiated ESC cannot be applied for therapeutic
purposes because of the risk of their malignant transformation. Therefore, main efforts should be focused on the
production of progenitor and highly differentiated cells suitable for transplantation derived from ESC.
Key words: human embryonic stem cells, permanent human ESC lines, genetic stability, mouse embryonic
stem cells
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