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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.

WHO International Clinical Trials Registry Platform


The World Health Organization (WHO) has created a new Web site to help researchers, doctors and
patients obtain reliable information on high-quality clinical trials. Now you can go to one website and search all registers to identify clinical trial research underway around the world!





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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, 2015

Telomeres are the protective caps on the ends of the strands of DNA
called chromosomes, which house our genomes.

 





 

 

Turning back aging in cells

A new procedure quickly and efficiently increases the length of human telomeres. Telomeres are the protective caps at the ends of chromosomes which when eroded, lead to aging and disease.

According to scientists at the Stanford University School of Medicine after treatment, cells behave as if they are much younger, multiplying with abandon in the laboratory dish rather than stagnating or dying. The new procedure involves using a modified type of RNA to generate large numbers of cells for biologic study and for use in drug development. Skin cells with telomeres lengthened by the procedure were able to induce cell divisions up to 40 times more than untreated cells.


The research may point to new ways to treat diseases caused by shortened telomeres.


Telomeres are the protective end caps on DNA strands — better known as chromosomes. In young people, telomeres are 8,000 to 10,000 nucleotides long, but continue to shorten with each cell division. When they reach a critical length they stop dividing and the cell dies. Most cell colonies in a lab cannot expand for more than a few cell division cycles.

Telomerase is expressed by all stem cells including those giving rise to sperm and eggs. The active component of telomerase is a naturally occurring enzyme called TERT, and the RNA used in this experiment contained the genetic code for TERT. This modified RNA was designed to reduce the cell's immune response, allowing TERT encoding to extend telomeres.  Researchers wanted telomeres to generate more cell divisions, which did occur. However, the TERT dissipated and was gone within 48 hours — the newly lengthened telomeres then began to progressively shorten with each cell division as they would normally.


The new technique had an important advantage — it is temporary.The treated cells don't go on to divide indefinitely as in cancer, which would make them too dangerous to use for any potential therapy in humans.


Researchers found that as few as three applications of the modified RNA introduced over a period of days, could significantly increase the length of telomeres in cultured human muscle and skin cells. A 1,000 nucleotide addition increased the length of the telomeres more than 10 percent. Skin cells divided about 28 more times than untreated cells, and muscle cells about three times more.


"We were surprised and pleased that modified TERT mRNA worked. Previous attempts to deliver mRNA-encoding TERT caused an immune response against telomerase. In contrast, our technique could not induce an immune response. Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse the telomere shortening that occurs over more than a decade in normal aging.

"This suggests that a treatment using our method could be brief and infrequent. This new approach paves the way toward preventing or treating diseases of aging. There are also highly debilitating genetic diseases associated with telomere shortening that could benefit from such a potential treatment."


John Ramunas, PhD research fellow, Microbiology and Immunology, Stanford School of Medicine


Helen M. Blau, Donald E. and Delia B. Baxter Foundation Professor and Director, Baxter Laboratory for Stem Cell Biology, who also is a member of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, and her colleagues became interested in telomeres from previous work. Her lab had shown that muscle stem cells of boys with Duchenne muscular dystrophy had telomeres that were much shorter than those of boys without the disease. This finding not only had implications for understanding how muscle stem cells function — or don't function — in making new muscle, it also helped explain the limited ability of laboratories to grow affected cells for study.

Researchers are now testing their new technique on other types of cells.

"This study is a first step toward the development of telomere extension to improve cell therapies and to possibly treat disorders of accelerated aging in humans," said John Cooke, MD, PhD. Cooke, a co-author of the study, formerly was a professor of cardiovascular medicine at Stanford, and now chair of cardiovascular sciences at the Houston Methodist Research Institute.


"We're working to understand more about the differences among cell types, and how we can overcome those differences to allow this approach to be more universally useful.

"One day it may be possible to target muscle stem cells in a patient with Duchenne muscular dystrophy, for example, to extend their telomeres. There are also implications for treating conditions of aging, such as diabetes and heart disease. This has really opened the doors to consider all types of potential uses of this therapy."

Helen M. Blau, Donald E. and Delia B. Baxter Foundation Professor and Director, Baxter Laboratory for Stem Cell Biology, who also is a member of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.


Abstract
Telomere extension has been proposed as a means to improve cell culture and tissue engineering and to treat disease. However, telomere extension by nonviral, nonintegrating methods remains inefficient. Here we report that delivery of modified mRNA encoding TERT to human fibroblasts and myoblasts increases telomerase activity transiently (24–48 h) and rapidly extends telomeres, after which telomeres resume shortening. Three successive transfections over a 4 d period extended telomeres up to 0.9 kb in a cell type-specific manner in fibroblasts and myoblasts and conferred an additional 28 ± 1.5 and 3.4 ± 0.4 population doublings (PD), respectively. Proliferative capacity increased in a dose-dependent manner. The second and third transfections had less effect on proliferative capacity than the first, revealing a refractory period. However, the refractory period was transient as a later fourth transfection increased fibroblast proliferative capacity by an additional 15.2 ± 1.1 PD, similar to the first transfection. Overall, these treatments led to an increase in absolute cell number of more than 1012-fold. Notably, unlike immortalized cells, all treated cell populations eventually stopped increasing in number and expressed senescence markers to the same extent as untreated cells. This rapid method of extending telomeres and increasing cell proliferative capacity without risk of insertional mutagenesis should have broad utility in disease modeling, drug screening, and regenerative medicine.—Ramunas, J., Yakubov, E., Brady, J. J., Corbel, S. Y., Holbrook, C., Brandt, M., Stein, J., Santiago, J. G., Cooke, J. P., Blau, H. M. Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells.

Other Stanford co-authors of the paper are postdoctoral scholars Jennifer Brady, PhD, and Moritz Brandt, MD; senior research scientist Stéphane Corbel, PhD; research associate Colin Holbrook; and Juan Santiago, PhD, professor of mechanical engineering.

The work was supported by the National Institutes of Health (grants R01AR063963, U01HL100397 U01HL099997 and AG044815), Germany's Federal Ministry of Education and Research, Stanford Bio-X and the Baxter Foundation.

Ramunas, Yakubov, Cooke and Blau are inventors on patents for the use of modified RNA for telomere extension.

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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