New procedures to obtain embryonic stem cells

Because of their remarkable potential for generating many different types of specialized cells, embryonic stem cells represent a most promising tool to develop novel therapeutic strategies to treat a great variety of human diseases. They are usually derived from early developing embryos, called blastocysts, before the implantation into the molther’s uterus. At this stage, the embryo is made of two types of cells: the trophoectoderm, the outer cell layer, which is necessary for the implantation and later forms the embryo-mother interface, and the inner cell mass, that will give rise to the entire organism. Embryonic stem cells to be used for research or therapeutic purposes are dissociated from the inner cell mass, a procedure that unavoidably destroys the embryo. For this reason, the use of such cells has been subject of intense ethical and political debate, leading to severe restriction of research in different countries, such as the United States and Italy. Two articles published in the last issue of Nature describe novel approaches to produce embryonic stem cells (1-3), which may partially overcome the ethical concerns related to the use of human embryos.

The second report (3) concerns a modification of the method, called nuclear transfer, which is used to produce cells that are genetically identical to a particular individual (this type of cells can be safely used for transplantation, because they will be not rejected by the donor patient). In this procedure, the nucleus of an ovocyte (a non-fertilised egg cell) is removed and replaced by that of cell taken from an adult donor (for example a blood or skin cell). In the egg environment the genetic material present in the adult donor nucleus is reprogrammed and an embryo-like blastocyst (embryoid) is formed, which can be used to isolate stem cells. Embryoid blastocysts are not usually able to develop into a full organism. However, the procedure is severely restricted by law because it may lead to human cloning. By exploiting methods derived from genetic engineering, the authors of this second article designed an altered nuclear transfer procedure. They inserted into egg cells the nuclei of donor cells defective for a gene (Cdx²), necessary for the generation of the trophoectoderm. As a consequence, the obtained embryoids have an inner cell mass, from which embryonic stem cells can be isolated, but are completely unable to implant into the uterus and, therefore, cannot develop further.

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