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New mouse model makes stem cells light up green

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Scientists at the University of Bonn have found a way to specifically mark multipotent stromal cells, making it possible to analyze their distribution pattern and their function in living organisms.

In order to examine a particular cell type, one must first be able to clearly distinguish it from others. Biologists and physicians have therefore developed sophisticated methods for the live labeling of specific cells. For multipotent stromal cells however, this has until now only been possible to a limited extent.

This is particularly unsatisfactory as these cells are a focal point of research interest, especially in regenerative medicine. For instance, it is known that they can become bone, fat or cartilage cells. Additionally, it is believed that they play a role in wound healing processes and in pathological events, such as those that occur during vascular calcification (arteriosclerosis).

“In all these development and disease processes however, there are still many unanswered questions, which is why we looked for a way to mark multipotent stromal cells in the living organism,” said Martin Breitbach, Ph.D., from the Institute of Physiology I at the University of Bonn.

To this end, the scientists searched for genetic information that is read frequently in the cells of interest, but is inactive in other cell types. They found what they were looking for in the so-called CD73 gene. They then generated transgenic mice, where expression of the CD73 gene results in green fluorescent labeling of the respective cell.

“As CD73 is mainly active in the multipotent stromal cells, these are marked by a green glow,” explained study co-author Kenichi Kimura, Ph.D.

This approach has, in principle, been established for many years. But until now there was no known adequate marker for multipotent stromal cells that was well-suited to distinguishing them from other cells. The dye-labeling made it possible to isolate these cells from the bone marrow. The scientists were then able to show that bone, fat and cartilage cells differentiate from a single multipotent stromal cell in the culture dish.

“Our method makes it possible to examine the cells in their original state,” Dr. Breitbach said. “In future studies, it will, for example, be possible to clarify directly in the living animal whether and how the stem cells migrate to the different organs in the case of injury or illness and what they do there.”

Chance discovery opens new perspectives

A result that the scientists themselves had not expected also opens up new research perspectives: In addition to the multipotent stromal cells, sinusoidal endothelial cells in the bone marrow are another cell type that appears to have increased CD73 activity.

The researchers were delighted about this discovery. It only became recently known that the maturation and distribution of hematopoietic stem cells are regulated by a variety of endothelial cell types. Sinusoidal endothelial cells probably play a key role here. But the underlying mechanisms are still rather puzzling because until recently they, too, could not be stained specifically and, thus, distinguished from the other endothelial cells within the bone marrow.

The scientists have now purified the various cell populations and characterized the genetic fingerprint of the multipotent stromal cells and the sinusoidal endothelial cells in detail. “These findings are extremely interesting,”, said Dr. Breitbach. “They provide deeper insights into these cell types and are a starting point for further studies.”

The current study, which in addition to the University of Bonn scientists included researchers from Oxford University, Tsukuba University and the Karolinska Institute Stockholm, was published in Cell Stem Cell.

Learn more:

https://www.uni-bonn.de/news/034-2018

DOI: 10.1016/j.stem.2018.01.008