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Very early-stage hESC lines created.

CAMBRIDGE, U.K., March 4, 2016 -- Scientists have for the first time shown that it is possible to derive from a human embryo so-called "naive" pluripotent stem cells that can develop into all human tissue other than the placenta.

Scientists at the University of Cambridge say the cells are a potential source of stem cells for use in regenerative medicine, and the technique could open up new avenues of research into disorders such as Down's syndrome.

The ability to derive naive stem cells has been possible for over thirty years from mouse embryos, using a technique developed at Cambridge, but this is the first time this has been possible from human embryos.

Human pluripotent stem cells for use in regenerative medicine or biomedical research come from two sources: embryonic stem cells, derived from fertilized egg cells discarded from IVF procedures; and induced pluripotent stem cells, where skin cells are reprogrammed to a pluripotent form.

However, these cells are already "primed" for differentiation into specific cell types. In contrast, all instructions have been erased in naive cells, which may make it easier to direct them into any cell type of interest.

Recently naive-like human induced pluripotent stem cells have been created by reprogramming but it has been unknown whether they can 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 and 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; and cells that form the yolk sac, which provides nutrients to the developing fetus; and the epiblast comprising the naive cells that will develop into the future body.

In the new research, scientists removed cells from the blastocyst at around day six and grew them individually in culture. By separating the cells, the researchers in effect stopped them talking to each other, preventing them from being steered down a particular path of development.

Until now it hasn't been possible to isolate these naive stem cells, even though the technology has exited to do it in mice for thirty years, leading some people to doubt it would be possible, But scientists extracted the cells and grew them individually in culture. Naive stem cells have many potential applications, from regenerative medicine to modelling human disorders.

Naive pluripotent stem cells in principle have no restrictions on the types of adult tissue into which they can develop. That means they may have promising therapeutic uses in regenerative medicine to treat devastating conditions that affect various organs and tissues, including the heart, brain and pancreas.

One of the more 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. Children with Down's syndrome are born with three copies of chromosome 21.

"Because we can separate the cells and culture them individually, we could potentially generate 'healthy' and 'affected' cell lines. said Jenny Nichols, joint senior author of the study. "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."

Citation: Ge Guo et al., "Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass," Stem Cell Reports, 2016; DOI: 10.1016/j.stemcr.2016.02.005


Contact: Jennifer Nichols,
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Title Annotation:Advanced Stem Cell Technology
Publication:Stem Cell Lab World
Date:Mar 21, 2016
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