20 May 2013

Mitalipov is not going to clone a person

Human embryonic stem cells were obtained for the first time by the method of somatic cell nuclei transfer

LifeSciencesToday based on materials from Oregon Health & Science University:
OHSU research team successfully converts human skin cells into embryonic stem cellsScientists at Oregon Health & Science University and the Oregon National Primate Research Center (ONPRC) have successfully reprogrammed human skin cells into embryonic stem cells capable of differentiating into any other type of cells in the body.

Stem cell–based therapies open up broad prospects for the development of regenerative medicine - the replacement of cells damaged as a result of injury or disease. Diseases that can be treated with cell therapy methods include Parkinson's disease, multiple sclerosis, heart disease and spinal cord injury.

The scientific breakthrough of the group led by Shoukhrat Mitalipov, PhD, senior researcher at ONPRC, is a continuation of the previous success – the transformation of monkey skin cells into embryonic stem cells – achieved in 2007. The results of the study are published in the journal Cell: Tachibana et al., Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer.

The technology used by Dr. Mitalipov, Paula Amato, MD, and their colleagues is a variant of the widely used somatic cell nuclear transfer (SCNT) method. It consists in transplanting the nucleus of a somatic cell containing the DNA of the organism into an egg cell from which the genetic material has been removed. As a result of the development of such an unfertilized egg, stem cells are formed.

The first stage of SCNT is the enucleation, or removal, of nuclear genetic material from a human egg. The egg is held by a pipette holder (left) and its chromosomes are visualized using a polarizing microscope. With the help of a laser, a hole is made in the egg shell (the pellucid zone), into which a smaller pipette is inserted (on the right). Then the chromosomes are sucked into the pipette and slowly removed from the egg (photo from the article in Cell)."A thorough study of stem cells obtained using this method has shown their ability to differentiate into several different cell types, including neurons, hepatocytes and cardiomyocytes, just as normal embryonic stem cells do.

In addition, since these reprogrammed cells can be obtained from the patient's nuclear genetic material, there is no risk of transplant rejection," explains Dr. Mitalipov. "Although much more needs to be done to develop safe and effective stem cell therapies, we believe this is a significant step forward in obtaining cells that can be used in regenerative medicine."

Another important aspect of this study is that it is not related to the use of embryos – the subject of ongoing ethical disputes.

The success of Mitalipov's group in reprogramming human skin cells is based on a series of studies of human and monkey cells. Previous unsuccessful attempts by several laboratories have shown that human eggs are apparently more fragile than eggs of other animal species. Therefore, the process of their development during reprogramming by already known methods was stopped until stem cells were obtained.

Scientists have found that the key factors responsible for the results of reprogramming by somatic cell nuclear transfer (SCNT) are the premature release of human oocytes from meiosis and their suboptimal activation. The optimized SCNT approach, developed to overcome these limitations, made it possible to obtain human NT-ESCs. Embryonic stem cells obtained by somatic cell nuclei transfer demonstrate a normal diploid karyotype and inherit the nuclear genome exclusively of somatic parent cells. Gene expression and differentiation profiles of human NT-ESCs are similar to those of ESCs obtained from embryos, which indicates an effective reprogramming of somatic cells into a pluripotent state (Fig. ohsu.edu ).To solve this problem, scientists have studied various alternative approaches, first developed on monkey cells, and then transferred to human cells.

They managed to find a way to "force" the cell to remain in the metaphase stage during the nuclear transplantation, which was the key to success. Metaphase is a stage of the natural process of meiosis, when before division the genetic material of the cell is arranged in the center. They found that maintaining the metaphase stage with chemicals throughout the entire nuclear transfer process prevents cell development from stopping and allows stem cells to be obtained.

However, while this method can be considered a method of cloning stem cells, commonly referred to as therapeutic cloning, it is unlikely to allow human clones to be obtained, that is, reproductive cloning. Long-term studies using the somatic cell nuclei transfer method have not led to success in obtaining monkey clones. Most likely, this also applies to the creation of human clones. In addition, the comparative fragility of human cells, as shown in this study, is an important factor that is likely to prevent the development of clones.

"Our research is aimed at obtaining stem cells for use in future methods of treating diseases," adds Dr. Mitalipov. "Advances in nuclear transfer often lead to public debate about the ethics of human cloning, but this is not our case, and we do not believe that our results can be used by others to expand the possibilities of human reproductive cloning."

Portal "Eternal youth" http://vechnayamolodost.ru20.05.2013

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