For the first time, scientists from the University of Cambridge have showed that is possible to derive naïve pluripotent stem cells from a human embryo. This is considered one of the most flexible types of stem cell, carrying the potential to develop into all types of human tissue aside from the placenta.

Stem cells

Mouse blastocyst at the pluripotent stage, when cells have the capacity to generate all of the cell types of the adult.
Credit: Jenny Nichols

There are two sources of human pluripotent stem cells that are being used in medicinal or biomedical research: embryonic stem cells and induced pluripotent stem cells.

Embryonic stem cells are derived from fertilized egg cells, cells that are commonly discarded from IVF procedures. Pluripotent stem cells are skin cells that are reprogrammed to a pluripotent form. Typically these cells have already been "primed" into specific cell types, however "naïve" cells have had all instructions erased in order to make it much easier to direct them to whatever type of cell is needed.

Naïve-like human induced pluripotent stem cells had recently been created by reprogramming, however it had been unknown whether they could also be obtained directly from the human embryo.

When an egg cell is fertilized by a sperm, it begins to divide and replicate before the embryo takes shape. Around day five, the embryonic cells cluster together to form a structure called the ‘blastocyst’. This occurs before implantation into the uterus. The blastocyst comprises three cell types: cells that will develop into the placenta and allow the embryo to attach to the womb; cells that form the ‘yolk sac’ which provides nutrients to the developing fetus; and the ‘epiblast’ comprising the naïve cells that will develop into the future body.

A new technique for pluripotent stem cells

In a study published in Stem Cell Reports, a team of scientists from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute were able to remove cells from the blastocyst at day six, and grow them individually in culture. They separated the eggs and thus stopped the "communication" between them to prevent them being steered to a particular path of development.

The research was supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Swiss National Science Foundation and the Wellcome Trust.

"Until now it hasn’t been possible to isolate these naïve stem cells, even though we’ve had the technology to do it in mice for thirty years – leading some people to doubt it would be possible," explains Ge Guo, the study's first author, “but we've managed to extract the cells and grow them individually in culture. Naïve stem cells have many potential applications, from regenerative medicine to modelling human disorders.”

In principle, these stem cells have no restrictions on what type of adult tissue they will develop into. Dr Jenny Nichols, joint senior author of the study, says that one of the most exciting applications of their new technique would be to study disorders that arise from cells that contain an abnormal number of chromosomes. Ordinarily, the body contains 23 pairs of identical chromosomes (22 pairs and one pair of sex chromosomes), but some children are born with additional copies, which can cause problems – for example, children with Down’s syndrome are born with three copies of chromosome 21.

“Even in many ‘normal’ early-stage embryos, we find several cells with an abnormal number of chromosomes,” explains Dr Nichols. “Because we can separate the cells and culture them individually, we could potentially generate ‘healthy’ and ‘affected’ cell lines. This would allow us to generate and compare tissues of two models, one ‘healthy’ and one that is genetically-identical other than the surplus chromosome. This could provide new insights into conditions such as Down’s syndrome.”

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