12 January 2012

Chimera monkeys

The first chimeric rhesus macaques were born at the Oregon National Primate Research Center

LifeSciencesToday based on materials from Oregon Health & Science University:
OHSU research demonstrates not all embryonic stem cells are equal; produces the world’s first primate chimeric offspringScientists from the Oregon National Primate Research Center (Oregon National Primate Research Center)

Oregon Health & Science University (Oregon Health & Science University) created the world's first chimera monkeys. The organisms of these three animals, normal and healthy, consist of a mixture of cells with six different genomes. This achievement opens up great opportunities for future research, since until now scientists have managed to create only chimeric mice. In addition, the researchers suggest the limited possibilities of embryonic stem cells grown in culture.


Roku (left) and Hex (right). Chimero refused to shoot this time :) – VM
photo by Oregon Health & Science University

Chimeric monkeys were born after scientists practically "glued" the cells of different rhesus macaque embryos and successfully implanted new mixed embryos into maternal organisms. The key to success was the use of embryo cells at a very early stage of development, when each individual embryonic cell is totipotent, that is, capable of giving rise to an entire animal, as well as the placenta and other life-supporting tissues. In this way, totipotent cells differ from pluripotent stem cells, which can differentiate into any type of body tissue, but cannot give rise to extraembryonic tissues or the whole organism.

"These cells never merge, but stay together and work together to form tissues and organs," says project leader Dr. Shoukhrat Mitalipov. "The opportunities for science are huge."

The first attempts of Dr. Mitalipov's group to create living chimeric monkeys by introducing cultured embryonic stem cells into monkey embryos – a generally recognized method for producing chimeric mice – ended in failure. Chimeric mice are extremely important for biomedical research, as they allow obtaining transgenic "knocked out" animals whose organisms lack certain genes, explains Dr. Mitalipov.


Diagram from an article in the journal Cell (Tachibana et al., Generation of Chimeric Rhesus Monkeys) – VM

Totipotent cells of early embryos are progenitors of all stem cells and can develop into an entire organism, including extraembryonic tissues such as the placenta. Pluripotent cells of the inner cell mass (ICM) are descendants of totipotent cells and can differentiate into any type of cells of the body, except extraembryonic tissues. The ability to reintroduce into the embryo of the recipient organism is a key feature of mouse totipotent and pluripotent cells, which makes it possible to obtain chimeric animals. Embryonic stem cells of rhesus monkeys and isolated ICMs are unable to be incorporated into the embryos of the recipient organism and develop into chimeras. Nevertheless, chimeric offspring can be obtained by aggregation of totipotent cells of embryos consisting of four cells. These results give an idea of the species specificity of primate embryos and suggest that obtaining chimeras using pluripotent cells is probably impossible.

According to him, primate embryos, unlike mouse embryos, seem to prevent the integration of cultured embryonic stem cells into them. In addition, the results of his research allow us to conclude that cultural embryonic stem cells of primates and humans, some of which are maintained in the laboratory for up to two decades, may not have the potential that cells inside a living embryo possess.

"We have to go back to basics," says Dr. Mitalipov. "It is necessary to study not only embryonic stem cells grown in culture, but also stem cells in the embryo. "It's too early to close the chapter on these cells." For example, he adds, compared to induced pluripotent stem (iPS) cells obtained by treating adult cells with relatively simple cocktails, cultured embryonic stem cells are currently considered the "gold standard".

"We can't model everything on mice," the scientist continues. "If we want to transfer stem cell therapy from laboratories to clinics and move from mice to humans, we need to understand what these cells can and cannot do in primates. We need to study them in the human body, including in human embryos." However, the scientist emphasizes, there is no practical use in creating human chimeras and no one has any intention to do this.

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12.01.2012

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