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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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A first: earliest stages of human stem cell lines

Scientists in the United Kingdom show it is possible to create so-called 'naïve' pluripotent stem cells from a human embryo. 'Naïve' pluripotent stem cells are the most flexible stem cells, and can develop into all human tissue except the placenta.

As well as a potential source of stem cells for use in regenerative medicine, this new technique could open up avenues for research into disorders such as Down's syndrome.

The ability to create naïve stem cells from mouse embryos has been possible for over thirty years. The technique was developed by Sir Martin Evans and Professor Matthew Kaufman during their time at Cambridge University in the UK. But, this is the first time naïve stem cells have been made from human embryos.

Human pluripotent stem cells considered for use in regenerative medicine or biomedical research to date come from two sources: (1) embryonic stem cells, from fertilised egg cells discarded from IVF procedures; and (2) induced pluripotent stem cells, or skin cells reprogrammed into a pluripotent form. However, both cell types are already "primed" to differentiate into specific cell types.

By contrast, naïve stem cells have all instructions erased, making them easier to change into any cell type necessary.

In December 2015, naïve-like induced human pluripotent stem cells were created via reprogramming mouse cells. But, it was unclear if such cells could be obtained directly from a human source. Cell Stem Cell.

When an egg cell is fertilised by a sperm, it divides and begins to replicate cells. Around day five, embryonic cells cluster together to form a structure called the 'blastocyst', just before implanting into the uterus. The blastocyst is made up of three cell types: one that will develop into the placenta and allow the embryo to attach to the womb; cells that form the 'yolk sac' and provide nutrients to the developing fetus; and 'epiblast' cells or the naïve cells that will develop into tissues of the body.

Research just published in the journal Stem Cell Reports, scientists from the Wellcome Trust-Medical Research Council within the Cambridge Stem Cell Institute, managed to remove cells from the blastocyst at around day six and grow them individually in culture. By separating the cells, they effectively stopped them from interacting with each other, preventing each cell from being sent down a particular path of development.

"Until now it hasn't been possible to isolate these naïve stem cells, even though we've had the technology to do so in mice for thirty years - leading some people to doubt it would be possible. 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."

Ge Guo PhD, Wellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, United Kingdom, and joint senior author of the study.

As naïve pluripotent stem cells have no developmental restrictions, they may have therapeutic use in regenerative medicine to treat devastating conditions. Particularly those medical conditions affecting organs and tissues with poor regenerative capacity, such as the heart, brain and pancreas.

One of the most exciting research avenues for their technique is in disorders resulting from abnormal numbers of chromosomes, adds Jennifer Nichols PhD, joint senior author and corresponding author for the study.

Ordinarily, each body cell contains 46 chromosomes (23 in each sex cell), but some children are born with additional copies. Children with Down's syndrome are born with three copies of chromosome 21.

Explains Dr Nichols: "Even in many 'normal' early-stage embryos, we find several cells with an abnormal number of chromosomes. Because we can separate the cells and culture them individually, we could potentially generate 'healthy' as opposed to '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."

In summary, these findings suggest that it is possible to suspend human developmental progression at the pre-implantation epiblast phase and propagate a self-renewing pluripotent state analogous to mouse ESCs (Boroviak et al., 2014, Brook and Gardner, 1997). Derivation of equivalent cell lines from non-human primates and formation of high-contribution chimeras would provide further validation. However, our results support the case for naive pluripotency in human development and may reconcile the long-running debate about the difference between PSCs from mice and men.

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

Reference: Guo, G et al. Naïve pluripotent stem cells derived directly from isolated cells of the human inner cell mass; Stem Cell Reports; 3 March 2016.

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Cell lines derived from human inner cell mass. (K Group) Immunofluorescence
of KLF17 and NANOG in D6 human Inner Cell Mass cells.
Image Credit: Geo Laboratory, Wellcome Trust-Medical Research Council, UK




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