Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Feeder-free system for maintaining pluripotency in embryonic stem cells pioneered

08.01.2004


A newly discovered molecule, nicknamed "BIO", safely maintains human embryonic stem cells in a pluripotent state. Its chemical structure is pictured above. The molecule was originally identified and purified from the purple dye extracted from the mollusk Hexaplex trunculus


Molecule developed from marine mollusk overcomes risks of current methods

Human embryonic stem cell (HESC) lines, or cultures, in the U.S. are not suitable for use in the budding field of regenerative medicine. Their creation using mouse feeder cells, a specialized growth medium, allows scientists to study their basic characteristics, but ultimately the HESCs are too risky to develop in applied medicine because mouse-associated viruses possibly contaminate them.

Now, Rockefeller University researchers in collaboration with two European scientists, have discovered a way around this problem: they’ve devised a system for maintaining existing or new human stem cell lines that excludes the need for troublesome mouse feeder cells.



The findings also have an intriguing underpinning. A marine animal belonging to the gastropod mollusk group is the original source of the compound now in use in the new feeder-free system. The natural molecule from which the new compound has now been synthesized has been harvested for over 2500 years from the creature, known as the red mollusk, as a coveted purple dye.

The identification of the small molecule, pharmacological inhibitor system in stem cells, led by Ali Brivanlou, Ph.D., head of the laboratory of molecular vertebrate embryology and his research associate, Noburo Sato, Ph.D., so far demonstrates superior stability over other methods designed to circumvent the need for mouse feeder cells. Nature Medicine features Brivanlou, Sato and their colleagues’ results in its January 2004 edition. And though still early in the team’s experiments, the stem cells appear to progress and differentiate normally after the compound is removed.

This new system for maintaining pluripotency could be a providential break for basic researchers and clinicians investigating the potential of HESCs, as it is a potential first step in providing an unlimited source of tissue transplant if HESCs’ potential comes to fruition in clinical medicine.

It works like this: a newly purified compound from the purple dye of marine red mollusks - called 6-bromoindirubin-3’-oxime, or by its working acronym, "BIO"- has been shown by Rockefeller scientists to indirectly activate a crucial gene expression mechanism, called the Wnt signaling pathway, in embryonic cells. Wnt signaling occurs when the new compound inhibits a specific protein kinase in embryonic cells, called GSK-3. This enzyme plays an essential role in many normal and disease states from development to neurodegenerative disorders. It is involved in numerous pathways including a highly conserved and important one called the Wnt signaling pathway. When GSK-3 is inactivated, Wnt is active. Chemical inhibition of GSK-3 thus mimics activation of Wnt and this keeps HESCs in an active, undifferentiated state - one of the crucial basic qualities of embryonic stem cells.

"We know precisely how this compound works - that is, on which enzymes and pathways - and that it is very controllable," says Brivanlou. "This knowledge makes the compound useful not only in stem cell research but also, as we are already seeing in the lab, numerous other research areas."

The challenges of HESC applied research are well known, along with the possible rewards. Cultured stem cells must be capable of self-renewal in an undifferentiated state in order to be truly useful.

Brivanlou, a comparative embryologist who studies the basic molecular aspects of very early vertebrate embryonic development, studies embryonic stem cells to determine whether they truly possess the unique qualities with which they are credited. He along with his scientific colleagues already developed a set of research standards for determining what qualifies as an embryonic stem cell, and what remains to be confirmed about them before clinical researchers safely can consider using them in human research. The standards were published in Science in May 2003.

He also revealed, in 2003, a set of genetic markers for human embryonic stem cells, showing that they do not share a majority of their gene expression patterns with mouse embryonic stem cells, and that there is a highly specific genetic definition of embryonic cells that makes them stem cells - in other words, those cells that can give rise to all body cell types. This research was published in Developmental Biology in July 2003.

These accomplishments were deliberate and systematic. The new system hailed from an unanticipated source. Early in 2003, Laurent Meijer, a biochemist from the Roscoff Marine Biology Institute in France, while on sabbatical at Rockefeller University, studying protein kinases involved in neurodegenerative diseases in Dr. Paul Greengard’s laboratory, asked Brivanlou to test a new compound he and his Greek colleague, Leandros Skaltsounis, had derived from naturally- occurring indirubin of Mediterranean mollusks. The two scientists wanted to know if this new compound could act as a potent and selective pharmacological inhibitor of GSK-3, and therefore as potentially useful against neurodegenerative disorders.

"Protein kinases are very promising targets for the discovery of new therapeutic agents," says Meijer. "In particular, pharmacological inhibitors of GSK-3 have great potential for application to treat Alzheimer’s disease and other neurodegenerative disorders, as well as sleep disorders and depression." (There are 520 protein kinases encoded in the human genome.)

Brivanlou and his colleague Alin Vonica, M.D., Ph.D. confirmed that the synthetic compound was able to mimic Wnt activation in the classical model of frog early embryonic development. In the process, Brivanlou also discovered that the compound safely could arrest differentiation of stem cells in frog embryos, while allowing them to continue to self-renew.

Thus far, Brivanlou has applied the BIO compound to frog, mouse and human stem cells, with favorable results.

Lynn Love | Rockefeller University
Further information:
http://www.rockefeller.edu/pubinfo/010504b.php

More articles from Life Sciences:

nachricht The hidden structure of the periodic system
17.06.2019 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht Tiny probe that senses deep in the lung set to shed light on disease
17.06.2019 | University of Edinburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

Im Focus: Tube anemone has the largest animal mitochondrial genome ever sequenced

Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.

The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....

Im Focus: Tiny light box opens new doors into the nanoworld

Researchers at Chalmers University of Technology, Sweden, have discovered a completely new way of capturing, amplifying and linking light to matter at the nanolevel. Using a tiny box, built from stacked atomically thin material, they have succeeded in creating a type of feedback loop in which light and matter become one. The discovery, which was recently published in Nature Nanotechnology, opens up new possibilities in the world of nanophotonics.

Photonics is concerned with various means of using light. Fibre-optic communication is an example of photonics, as is the technology behind photodetectors and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Novel communications architecture for future ultra-high speed wireless networks

17.06.2019 | Information Technology

Climate Change in West Africa

17.06.2019 | Earth Sciences

Robotic fish to replace animal testing

17.06.2019 | Ecology, The Environment and Conservation

VideoLinks
Science & Research
Overview of more VideoLinks >>>