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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 in 1993 as a first generation internet teaching tool consolidating human embryology teaching for first year medical students.

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 SemestersFemale Reproductive SystemFertilizationThe Appearance of SomitesFirst TrimesterSecond TrimesterThird TrimesterFetal 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 HemispheresEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterDevelopmental Timeline
Click weeks 0 - 40 and follow fetal growth
Search artcles published since 2007

December 5, 2012--------News Archive Return to: News Alerts


These are endothelial cells derived by indirect lineage
conversion from human fibroblasts (skin cells).

Cell nuclei are in blue
Proteins that are hallmarks of endothelial cells are green and red.





WHO Child Growth Charts

       


Salk Scientists Develop Faster, Safer Production of Stem Cells

The new method boosts cell yields and increases safety, helping to get another step closer to regenerative medicine

A new method for generating stem cells from mature cells promises to boost stem cell production in the laboratory, helping to remove a barrier to regenerative medicine therapies that would replace damaged or unhealthy body tissues.


The technique, developed by researchers
at the Salk Institute for Biological Studies,
allows for the unlimited production of
stem cells and their derivatives as well as
reduces production time by more than half,
from nearly two months to two weeks.


"One of the barriers that needs to be overcome before stem cell therapies can be widely adopted is the difficulty of producing enough cells quickly enough for acute clinical application," says Ignacio Sancho-Martinez, one of the first authors of the paper and a postdoctoral researcher in the laboratory of Juan Carlos Izpisua Belmonte, the Roger Guillemin Chair at the Salk Institute.

They and their colleagues, including Fred H. Gage, professor in Salk's Laboratory of Genetics, have published a new method for converting cells in this week's Nature Methods.

Stem cells are valued for their "pluripotency," the ability to become nearly any cell in the body. Stem cells for research and clinical uses are derived in two ways, either directly from cells young enough to still be pluripotent, or from mature cells that have been "reprogrammed" to be pluripotent.

The first kind are called "embryonic stem cells," (ESCs) even though the term is a misnomer. They are actually taken from blastocysts, the hollow bundle of cells approximately the size of a tip of a pin that is formed by a fertilized egg after five days of cell division. After a blastocyst implants in the uterus, the embryo stage begins.


Aside from the well-known ethical controversies,
ESCs have a less discussed problem:
Tissues grown from ESCs may trigger immune
reactions when they are transplanted into patients.

In order to overcome both ethical and medical
concerns, scientists learned how to coax mature cells
(called "somatic cells") that had differentiated into
particular types of tissue back to their pluripotent state.

These so-called "induced pluripotent stem cells,"
or iPSCs, set off whole new rounds of research,
including a third way to get desired cell types.

As it turns out, iPSCs have their own problems.
They take a long time to create, in a highly inefficient
process that can take up to two months to complete.

First, somatic cells must be reprogrammed to iPSCs,
which takes considerable time and effort. Then,
the iPSCs have to be differentiated into specific cell
lines prior to therapeutic application. Far worse,
they can sometimes develop into tumors,
called teratomas, which can be cancerous.


Knowing this, scientists wondered if it might not be necessary to go all the way back to the blank slate of a pluripotent stem cell. Key to this idea is that pluripotent stem cells do not immediately grow into particular cells. They go through intermediate progenitor phases where they become "multipotent," and can only develop into cell types within a certain cellular lineage. While a pluripotent cell can become nearly any cell in the body, a multipotent blood cell, for example, can become red or white blood cells or platelets, but not distant lineages such as neurons.

Thus, in order to avoid the potential problems of working with iPSCs, scientists developed the technique of "direct lineage conversion." Unlike the familiar scenario, in which a pluripotent cell would divide and generate all different cell types of an adult individual, in direct lineage conversion one somatic cell is turned into just one other cell type, thus, for example, one skin cell becomes one muscle cell, but nothing else.

While this technique is effective, the Salk team and their colleagues wondered if there might be a modification that could be both more efficient and safer.

"Beyond the obvious issue of safety, the biggest consideration when thinking about stem cells for clinical use is productivity," says Salk post doctoral researcher Leo Kurian, a first co-author on the paper.

The team developed a new technique, which they dubbed "indirect lineage conversion" (ILC). In ILC, as explained in detail in Nature Methods, somatic cells are pushed back to an earlier state suitable for further specification into progenitor cells.

ILC has the potential to generate multiple lineages once cells are transferred to the team's specially developed chemical environment. Most importantly, ILC saves time and reduces the risk of teratomas by not requiring iPSC generation. Instead, somatic cells are directed to become the progenitor cells of particular lineages. "We don't push them to zero, we just push them a bit back," Sancho-Martinez says.

Using ILC, the group reprogrammed human fibroblasts (skin cells) to become angioblast-like cells, the progenitors of vascular cells. These new cells could not only proliferate, but also further differentiate into endothelial and smooth muscle vascular lineages. When implanted in mice, these cells integrated into the animals' existing vasculature.

"One of the long-term hopes for stem cell research is exemplified by this study, where stem cells would self-assemble into 3D structures and then integrate into existing tissues," says Juan Carlos Izpisua Belmonte.


While such clinical use may be years away,
this new method has several advantages
over current techniques, he explains.

It is safer, since it does not seem to produce
tumors or other undesirable genetic changes,
and results in much greater yield than other methods.

Most important, it is faster, and this is part of what
makes it not only more productive, but less risky.


"Generally it can take up to two months to create iPSCs and their differentiated derivatives, which increases the chances for mutations to take place," says Emmanuel Nivet, the third of the first co-authors. "Our method takes only 15 days, so we've substantially decreased the chances for spontaneous mutations to take place."

Other researchers on the study were: Aitor Aguirre, Krystal Moon, Caroline Pendaries, Cecile Volle-Challier, Francoise Bono, Jean-Marc Herbert, Julian Pulecio, Yun Xia, Mo Li, Nuria Montserrat, Sergio Ruiz, Ilir Dubova, Concepcion Rodriguez, Ahmet M. Denli, Francesca S. Boscolo, Rathi D. Thiagarajan, Jeanne F. Loring and Louise C. Laurent.

The work was supported by: the California Institute for Regenerative Medicine; the F.M. Kirby Foundation; National Institutes of Health; the Hartwell Foundation; the Millipore Foundation; the Esther O'Keeffe Charitable Trust Foundation; Fundacion Cellex; the G. Harold and Leila Y. Mathers Charitable Foundation; The Leona M. and Harry B. Helmsley Charitable Trust, Sanofi; and the Ministerio de Economia y Competitividad.

About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Original article: endothelial cells derived by indirect lineage conversion from human fibroblasts (skin cells)