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Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than one million visitors each month.

Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive Feb 6, 2014

 

To earn the name pluripotent, cells have to be able to turn into all cell types —
demonstrated by fluorescently tagging each cell, then injecting them into a mouse embryo.
If the transferred cells are pluripotent, they glow in every tissue of the resultant mouse.

Image credit: Riken Center for Developmental Biology, Kobe, Japan






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How to make pluripotent stem cells easily

Dr Haruko Obokata, of the Riken Centre for Developmental Biology in Japan, has shown how stem cells can be made quickly by dipping red blood cells into a mildly acidic solution. Stem cells are the cells that can transform into any tissue and are already in clinical trials for eye, heart and brain treatments.

Dr Dusko Ilic, a reader in stem cell science at Kings College London comments: "The approach is indeed revolutionary. It will make a fundamental change in how scientists perceive the interplay of environment and genome."  But added: "It does not bring stem cell-based therapy closer [until tested by various labs]. We will need to use the same precautions for the cells generated in this way as for the cells isolated from embryos or reprogrammed with a standard method."

Dr Obokata's latest development is published in the journal Nature, and explains how her discovery has the potential to make stem cell technology cheaper, faster and even safer.


The human body is built of cells, each with a specific identity which is fixed. However, stem cells are not bound by this rule and can become any type of cell.

They have become a major field of research in medicine for their potential to regenerate cells damaged by injury or disease - or perhaps missing altogether through developmental error.


Aborted embryos are one source of stem cells that are under continual ethical challenge as a source for use in experimental medicine — as are excess embryos left over from laboratory assisted reproduction fertilizations donated to science. However, Nobel prize winning research by Shinya Yamanaka in 2006, has shown that a small number of skin cells from mice, when activated, were able to be reprogrammed into immature stem cells, which then went on to grow into all types of cells within the body. Since his discovery, more and more science has been attempting to reclaim the inherent stem cell quality of any cell that may be easily harvested without ethical challenge.


Now, Obokata's study shows that mildly shocking blood cells with a citric acid (lemon juice) bath can trigger blood cells to transform into stem cells. Dr Obokata named these cella after the process by which they are harvested: STAP (stimulus-triggered acquisition of pluripotency) cells.


Haruko Obokata works in the Riken Centre for Developmental Biology in Japan — and she too was "really surprised" that cells could respond to this change in their environment so radically, adding: "It's exciting to think about the new possibilities these findings offer us, not only in regenerative medicine, but for cancer as well."


The breakthrough was achieved in mouse blood cells, but research is now taking place to achieve the same results with human blood.


Chris Mason, professor of regenerative medicine at University College London, speaking to the BBC said that if the procedure also works in humans "the age of personalised medicine would have finally arrived. I thought - 'my God that's a game changer!' It's a very exciting. It looks a bit too good to be true, but [given] the number of experts who have reviewed and checked this, I'm sure that it is."


"If this works in people as well as it does in mice, it looks faster, cheaper and possibly safer than other cell reprogramming technologies - personalised reprogrammed cell therapies may now be viable."

Chris Mason, professor of regenerative medicine, University College London


Currently in age-related macular degeneration, which causes sight loss, it takes 10 months to go from a patient's skin sample to a therapy that could be injected into that patient's eye — and at a huge cost. Prof Mason believes using Obokata's technique, weeks could be knocked off that 10 months, saving time and money using her cheaper technology to create a patient's own personalized stem cells.

Dr Haruko Obokata nearly gave up on her project when fellow researchers couldn't believe what she found. It took Obokata, a young stem-cell biologist, five years to develop the method and persuade Sasai and others that it works. “Everyone said it was an artefact [an undesired alteration in data, introduced by a technique and/or technology}— there were some really hard days,” said Obokata. Her manuscript was rejected multiple times. So she made pluripotent cells by stressing T cells, a type of white blood cell, whose maturity as a cell can be clearly read from gene changes made throughout its development. She also caught the conversion of T cells to pluripotent cells on video.

Other scientists have reported making pluripotent cells from mammalian body cells. Catherine Verfaillie, a molecular biologist at the University of Minnesota in Minneapolis in 2002, felt she had created multipotent adult progenitor cells in her published article in the journal Nature, July 2, 2002. But other researchers had difficulty reproducing her findings — the gold standard proof for experiments.

Obokata started her current project in the laboratory of tissue engineer Charles Vacanti at Harvard University in Cambridge, Massachusetts, by looking at cells that Vacanti’s group thought to be pluripotent cells they had isolated from the human body. But Obokata suggested a different explanation for that incident of plurpotency — that those pluripotent cells were created after the body’s cells endured physical stress. “The generation of these [pluripotent] cells is essentially Mother Nature’s way of responding to injury,” says Vacanti, now a co-author of Obokata's latest paper.

Obokata got the idea that stressing cells might make them pluripotent after noticing that squeezing cells through a capillary tube, shrank the cells to a size similar to that of stem cells. She decided to then apply different kinds of stress to cells, such as heat, starvation, a high-calcium environment. Three stressors — a bacterial toxin that perforates the cell membrane, exposure to low pH, and physical squeezing — coaxed cells into pluripotency.


But to earn the name pluripotent, cells have to be able to turn into all cell types — demonstrated by fluorescently tagging each cell, then injecting them into a mouse embryo. If the transferred cells are pluripotent, they glow in every tissue of the resultant mouse.


One surprising finding is that the Obokata STAP cells can also form placental tissue. Neither iPS cells nor embryonic stem cells can do this. Such a result alone could make cloning cells much easier, says mouse-cloning pioneer Teruhiko Wakayama of the University of Yamanashi, Japan. Wakayama was one sciencetist who initially thought the Obokata project was a “huge effort in vain.”

Currently, cloning requires extracting unfertilized eggs, transferring a donor nucleus into an unfertilized egg, in vitro cultivation of that embryo under a microscope in a laboratory, and then transfer of "a normal looking" embryo into a surrogate mother. If STAP cells can create their own placenta, they could possibly be transferred directly into a surrogate mother. Wakayama is cautious, however, saying that the idea is currently in the“dream stage.”

Obokata has already reprogrammed a dozen cell types from brain, skin, lung and liver cells. On average, 25% of tested cells survived the stress and 30% of those converted to pluripotent cells — already a higher proportion than the roughly 1% conversion rate of iPS [induced pluripotent stem] cells, which take several weeks to become pluripotent. Obokata now wants to examine how reprogramming in the body is related to the activity of stem cells. She is also trying to make the method work in cells from adult mice as well as in humans.


“The findings are important to understand nuclear reprogramming. From a practical point of view toward clinical applications, I see this as a new approach to generate iPS-like cells.”

Shinya Yamanaka, pioneered iPS [induced pluripotent stem]cell research and won the Nobel Prize in 2012. He and others who refined his technique, added 4 genes to adult cells to turn them pluripotent stem cells.


And Prof Lovell-Badge adds: "It is going to be a while before the nature of these cells are understood, and whether they might prove to be useful for developing therapies, but the really intriguing thing to discover will be the mechanism underlying how a low pH shock triggers reprogramming - and why it does not happen when we eat lemon or vinegar or drink cola?"

Abstract
Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency (STAP), which requires neither nuclear transfer nor the introduction of transcription factors. In STAP, strong external stimuli such as a transient low-pH stressor reprogrammed mammalian somatic cells, resulting in the generation of pluripotent cells. Through real-time imaging of STAP cells derived from purified lymphocytes, as well as gene rearrangement analysis, we found that committed somatic cells give rise to STAP cells by reprogramming rather than selection. STAP cells showed a substantial decrease in DNA methylation in the regulatory regions of pluripotency marker genes. Blastocyst injection showed that STAP cells efficiently contribute to chimaeric embryos and to offspring via germline transmission. We also demonstrate the derivation of robustly expandable pluripotent cell lines from STAP cells. Thus, our findings indicate that epigenetic fate determination of mammalian cells can be markedly converted in a context-dependent manner by strong environmental cues.

Nature 505, 641–647 (30 January 2014) doi:10.1038/nature12968

Received 10 March 2013 Accepted 20 December 2013 Published online 29 January 2014

Corresponding authors
Haruko Obokata, Teruhiko Wakayama, Yoshiki Sasai, Koji Kojima, Martin P. Vacanti, Hitoshi Niwa, Masayuki Yamato & Charles A. Vacanti