Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New way out: Researchers show how stem cells exit bloodstream

29.06.2016

Researchers at North Carolina State University have discovered that therapeutic stem cells exit the bloodstream in a different manner than was previously thought. This process, dubbed angiopellosis by the researchers, has implications for improving our understanding of not only intravenous stem cell therapies, but also metastatic cancers.

When white blood cells need to get to the site of an infection, they can exit the bloodstream via a process called diapedesis. In diapedesis, the white blood cell changes its shape in order to squeeze between or through the epithelial cells that form the walls of the blood vessel.


A stem cell exits the bloodstream through angiopellosis.

Credit: Alice MacGregor Harvey, NC State University

Diapedesis is a well-understood process, and researchers believed that other types of cells, like therapeutic stem cells or even metastatic cancer cells, exited blood vessels in a similar way - with the cells pushing or squeezing themselves out.

But a group of researchers led by Ke Cheng, associate professor of molecular biomedical sciences at NC State with a joint appointment in the NC State/UNC-Chapel Hill Department of Biomedical Engineering, found that these stem cells behaved differently.

Therapeutic stem cells share the same ability to exit the bloodstream and target particular tissues that white blood cells do. But the precise way that they did so was not well understood, so Cheng and his team utilized a zebrafish model to study the process.

The genetically modified zebrafish embryos were transparent and had fluorescently marked green blood vessels. Researchers injected the embryos with white blood cells and cardiac stem cells from humans, rats and dogs. These cells had all been marked with a red fluorescent protein.

Through time-lapse three-dimensional light sheet microscopic imaging, Cheng and his team could trace the progress of these cells as they left the blood vessel. The white blood cells exited via diapedesis, as expected. When stem cells exited the blood vessel, however, the endothelial cells lining the vessel actively expelled them. Membranes surrounding the endothelial cells on either side of the stem cell stretched themselves around the stem cell, then met in the middle to push the stem cell out of the vessel.

"When you're talking about diapedesis, the white blood cell is active because it changes its shape in order to exit. The endothelial cells in the blood vessel are passive," Cheng says. "But when we looked at therapeutic stem cells, we found the opposite was true - the stem cells were passive, and the endothelial cells not only changed their shape in order to surround the stem cell, they actually pushed the stem cells out of the blood vessel. We've named this process angiopellosis, and it represents an alternative way for cells to leave blood vessels."

The researchers found two other key differences between angiopellosis and diapedesis: one, that angiopellosis takes hours, rather than minutes, to occur; and two, that angiopellosis allows more than one cell to exit at a time.

"Angiopellosis is really a group ticket for cells to get out of blood vessels," Cheng says. "We observed clusters of cells passing through in this way. Obviously, this leads us to questions about whether other types of cells, like metastatic cancer cells, may be using this more effective way to exit the bloodstream, and what we may need to do to stop them."

###

The research is published in Stem Cells. Tyler Allen, a graduate student in the comparative biomedical sciences program, is the first author of the paper. The research was supported by the National Institutes of Health and the American Heart Association.

-peake-

Note to editors: An abstract of the paper follows

"Angiopellosis as an alternative mechanism of cell extravasation"

DOI: 10.1002/stem.2451

Authors: Tyler Allen, Jhon Cores, Adam Vandergriff, Ke Cheng, NC State Department of Molecular Biomedical Sciences and joint Department of Biomedical Engineering, NC State and UNC-Chapel Hill; David Gracieux, Maliha Talib, Debra Tokarz, M. Taylor Hensley, James B.M. de Andrade, Phuong-Uyen Dinh, Jeffrey Yoder, North Carolina State University: Junnan Tang, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

Published: Online in Stem Cells

Abstract:

Stem cells possess the ability to home in and travel to damaged tissue when injected intravenously. For the cells to exert their therapeutic effect, they must cross the blood vessel wall and enter the surrounding tissues. The mechanism of extravasation injected stem cells employ for exit has yet to be characterized. Using intravital microscopy and a transgenic zebrafish line tg(Fli1a:egpf) with GFP-expressing vasculature, we documented the detailed extravasation processes in vivo for injected stem cells in comparison to white blood cells (WBCs). While WBCs left the blood vessels by the standard diapedesis process, injected cardiac and mesenchymal stem cells underwent a distinct method of extravasation that was markedly different from diapedesis. Here, the vascular wall undergoes an extensive remodeling to allow the cell to exit the lumen, while the injected cell remains distinctively passive in activity. We termed this process Angio-pello-sis, which represents an alternative mechanism of cell extravasation to the prevailing theory of diapedesis.

Media Contact

Tracey Peake
tracey_peake@ncsu.edu
919-515-6142

 @NCStateNews

http://www.ncsu.edu 

Tracey Peake | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>