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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 Jan 26, 2014

Upper left is the mouse bone growth plate from which mouse skeletal stem cells (mSSCs)
are isolated into seven downstream progenitor cells. Researchers then identified a single
type of cell that could form into all of these skeletal elements. They then identified all the
genetic switches needing to be flipped in order to recreate all these highly specialized cells.
This information may lead to the ability to convert muscle or fat cells into types of skeletal tissue.
Image Credit: Cell.

 






 

 

Turning stem cells into bones, cartilage & stroma

Researchers at the Stanford University School of Medicine have discovered the stem cell in mice that gives rise to bone, cartilage, and a key part of bone marrow called the stroma.

And in addition, they have charted the chemical signals that can create skeletal stem cells and steer their development into each of those specific tissues. This discovery sets the stage for a wide range of potential therapies for skeletal disorders such as bone fractures, brittle bones, osteosarcoma and damaged cartilage. A paper describing these findings is published in Cell.

"Millions of times a year, orthopedic surgeons see torn cartilage in a joint and have to take it out because cartilage doesn't heal well, but that lack of cartilage predisposes the patient to arthritis down the road," said Michael Longaker MD, a professor of plastic and reconstructive surgery at Stanford and a senior author of the paper.


"This research raises the possibility that we can create new skeletal stem cells from patients' own tissues and use them to grow new cartilage."

Michael Longaker MD, co-director, Stanford Institute for Stem Cell Biology and Regenerative Medicine.


The researchers started by focusing on rapidly dividing cells at the ends of mouse bones, and showed that these cells could form all parts of bone: the bone itself, cartilage and the stroma - the spongy tissue at the center of bones that helps hematopoietic stem cells turn into blood and immune cells. With extensive effort, they then identified a single type of cell that could form all of these skeletal elements. The scientists went even further, mapping the developmental skeletal stem cells in order to track exactly how cells changed into intermediate progenitor cells and from there into each type of skeletal tissue.

"Mapping the tree led to an in-depth understanding of all the genetic switches that have to be flipped in order to give rise to more specific progenitor cells and eventually into highly specialized cells," said Charles Chan PhD. With that information, researchers were able to identify factors that, provided in the right amount at the right time, steer skeletal stem cells into bone, or cartilage or stromal cells.

"If this can be translated into humans, we then have a way to isolate skeletal stem cells and rescue cartilage from wear and tear or aging, repair bones that have nonhealing fractures and renew bone marrow in those who have had it damaged," added Irving Weissman, MD, professor of pathology and of developmental biology, who directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine.


In addition to learning how to create bone, cartilage and stromal cells out of skeletal stem cells, the researchers found out how to create skeletal stem cells themselves out of fat or muscle cells.


The ability to reprogram mature fat cells directly into skeletal stem cells through the application of specific signals "was really interesting and quite unexpected," said Longaker, who is also the Deane P. and Louise Mitchell Professor in the School of Medicine. It raises fascinating possibilities for future therapies, he added. "Right now, if you have lost a significant portion of your leg or jaw bones, you have to borrow from Peter to pay Paul in that you have to cut another bone like the fibula into the shape you need, move it and attach it to the blood supply. But if your existing bone is not available or not sufficient, using this research you might be able to put some of your own fat into a biomimetic scaffold, let it grow into the bone you want in a muscle or fat pocket, and then move that new bone to where it's needed."


"In this research we now have a Rosetta stone that should help find the human skeletal stem cells and decode the chemical language used to steer their development. The pathways in humans should be very similar and share many of the major genes used in the mouse skeletal system."

Charles Chan PhD, shares lead authorship on the paper.


Highlights
•Bone, cartilage, and stroma are derived from clonal, lineage-restricted progenitors
•We defined a postnatal skeletal stem cell (mSSC) and seven downstream progenitors
•Skeletal progenitor fate can be directed from bone to cartilage and vice versa
•Manipulation of mSSC niche signaling can induce de novo bone or cartilage formation

Summary
How are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues.

Other Stanford co-authors of the paper are Calvin Kuo, MD, PhD, professor of medicine; Kelley Yan, MD, PhD, instructor of medicine; former instructor Debashis Sahoo, PhD; research associate Jun Seita; postdoctoral scholars Adrian McArdle, Rahul Sinha, Ruth Tevlin, Wan-Jin Lu, Kshemendra Senarath-Yapa, and Michael Chung; graduate students Rosalynd Upton, Graham Walmsley and Andrew Lee; and research assistants Justin Vincent-Tompkins, Taylor Wearda, Owen Marecic and Misha Tran.

Charles Chan PhD, shares lead authorship of the paper with postdoctoral scholar David Lo MD, graduate student James Chen and research assistant Elly Eun Young Seo.

This work was supported by the National Institutes of Health, the Virginia and D.K. Ludwig Fund for Cancer Research, the Thomas and Stacey Siebel Foundation, the Prostate Cancer Foundation, the California Institute for Regenerative Medicine, the Oak Foundation, the Hagey Laboratory for Pediatric Regenerative Medicine, the Gunn/Olivier Research Fund, the Stinehart-Reed Fund, the Stanford Medical Scientist Training Program, the Stanford University Transplant and Tissue Engineering Center of Excellence, the Plastic Surgery Foundation/Plastic Surgery Research Council, the American Society of Maxillofacial Surgeons, the Burroughs Wellcome Fund, and the Anonymous Donor Skeletal Stem Cell Research Fund.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://med.stanford.edu/school.html. The medical school is part of Stanford Medicine, which includes Stanford Health Care and Lucile Packard Children's Hospital Stanford. For information about all three, please visit http://med.stanford.edu.

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