For the first time in the lab, researchers see stem cells take key step toward development

May 30, 2014

CHAMPAIGN, Ill. -- The gap between stem cell research and regenerative medicine just became a lot narrower, thanks to a new technique that coaxes stem cells, with potential to become any tissue type, to take the first step to specialization. It is the first time this critical step has been demonstrated in a laboratory.

University of Illinois researchers, in collaboration with scientists at Notre Dame University and the Huazhong University of Science and Technology in China, published their results in the journal Nature Communications.

"Everybody knows that for an embryo to form, somehow a single cell has a way to self-organize into multiple cells, but the in vivo microenvironment is not well understood," said study leader Ning Wang, a professor of mechanical science and engineering at the U. of I. "We want to know how they develop into organized structures and organs. It doesn't happen by random chance. There are biological rules that we don't yet understand."

During fetal development, all the specialized tissues and organs of the body form out of a small ball of stem cells. First, the ball of generalized cells separates into three different cell lines, called germ layers, which will become different systems of the body. This crucial first step has eluded researchers in the lab. No one has yet been able to induce the cells to form the three distinct germ layers, in the correct order - endoderm on the inside, mesoderm in the middle and ectoderm on the outside. This represents a major hurdle in the application of stem cells to regenerative medicine, since researchers need to understand how tissues develop before they can reliably recreate the process.

"It's very hard to generate tissues or organs, and the reason is that we don't know how they form in vivo," Wang said. "The problem, fundamentally, is that the biological process is not clear. What is the biological environment that controls this, so they can become more organized and specialized?"

Wang's team demonstrated that not only is it possible for mouse embryonic stem cells to form three distinct germ layers in the lab, but also that achieving the separation requires a careful combination of correct timing, chemical factors and mechanical environment. The team uses cell lines that fluoresce in different colors when they become part of a germ layer, which allows the researchers to monitor the process dynamically.

The researchers deposited the stem cells in a very soft gel matrix, attempting to recreate the properties of the womb. They found that several mechanical forces played a role in how the cells organized and differentiated - the stiffness of the gel, the forces each cell exerts on its neighbors, and the matrix of proteins that the cells themselves deposit as a scaffolding to give the developing embryo structure.

By adjusting the mechanical environment, the researchers were able to observe how the forces affected the developing cells, and found the particular combination that yielded the three germ layers. They also found that they could direct layer development by changing the mechanics, even creating an environment that caused the layers to form in reverse order.

Now, Wang's group is working to improve their technique for greater efficiency. He hopes that other researchers will be able to use the technique to bridge the gap between stem cells and tissue engineering.

"It's the first time we've had the correct three-germ-layer organization in mammalian cells," Wang said. "The potential is huge. Now we can push it even further and generate specific organs and tissues. It opens the door for regenerative medicine."
-end-
Editor's note:

To contact Ning Wang, call 217-265-0913; email nwangrw@illinois.edu.

The paper, "Generation of Organized Germ Layers From a Single Mouse Embryonic Stem Cell," is available online at http://www.nature.com/ncomms/2014/140530/ncomms5000/full/ncomms5000.html.

University of Illinois at Urbana-Champaign

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.