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New research shows how stem cells exit bloodstream.

RALEIGH, N.C., June 28, 2016--Therapeutic stem cells exit the bloodstream in a different manner than was previously thought, new research shows.

This process, dubbed angiopellosis by the researchers at North Carolina State University, 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.

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 researchers here 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 the scientists used 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, they 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.

In 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.

But with therapeutic stem cells, the opposite is true. The stem cells were passive, and the endothelial cells not only changed their shape to surround the stem cell, they actually pushed the stem cells out of the blood vessel. Angiopellosis represents an alternative way for cells to leave blood vessels.

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

There are questions: are other types of cells, like metastatic cancer cells, using this more effective way to exit the bloodstream? And what needs to be done to stop them?

Citation: Tyler A. Allen et al., "Angiopellosis as an Alternative Mechanism of Cell Extravasation," Stem Cells, 2016; DOI: 10.1002/stem.2451

Abstract: Contact: Ke Cheng,

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Title Annotation:Basic Research
Publication:Stem Cell Research News
Date:Jul 4, 2016
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