Scientists at the University of California San Francisco have discovered a new function of lungs: They make blood — which leads to a new wellspring of stem cells as well.
The astonishing breakthrough comes courtesy of refinement to microscopic video imaging that allows researchers to probe individual cells within blood vessels of a living host's lungs — in this case, mice lungs.
The findings have far-reaching implications for human study: Researchers were surprised to find that not only did the lungs produce more blood cells, they did so in volumes that indicated more than half of all platelets in circulation — critical for clotting — are produced by the lungs.
The significance for the blood stem cells also was compelling. The newly discovered pool of stem cells is capable of restoring blood production when bone marrow stem cells are depleted. This could lead to novel approaches to treating leukemia, a cancer of white blood cells that crowds out red blood cells, and bone cancer, which destroys the body's ability to manufacture red blood cells.
“This finding definitely suggests a more sophisticated view of the lungs — that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said pulmonologist Mark R. Looney, a professor of medicine and of laboratory medicine at the University of California, and the research's senior author. “What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.” The report was published online at Nature.com.
The new imaging approach allowed scientists to examine interactions between the immune system and platelets in the lungs. While following the interactions, they discovered a surprisingly large population of cells that produce platelets — called megakaryocytes. Though these cells were observed in the lungs previously it was generally though that they exist primarily in bone marrow.
Researchers were baffled — and more detailed imaging followed. Once they zeroed in on these cells, they soon realized that they not only took up residence in the lungs, they also were producing 10 million platelets per hour there — evidence that more than half of platelet production actually occurs in the lungs (in the mice models).
To be able to track blood stem cells and blood production, researchers transplanted donor lungs to mice with fluorescent-dye-tinted megakaryocytes. They followed the fluorescent cells as they traveled to the new lungs.
In another experiment, scientists wanted to determine if lungs that already had these platelet producers imbedded would spur platelet production in mice with low platelet counts, so they transplanted lungs with fluorescent-tinted megakaryocytes into mice predetermined to have low platelet counts. The transplanted lungs quickly sprung into action and restored normal platelet levels.
In yet another experiment, researchers transplanted healthy lungs with all cells fluorescently tinted into mice without bone marrow blood stem cells. The fluorescent marker cells quickly traveled to the damaged bone marrow and began production of myriad cells — including T cells, which are key immune cells.
The exact mechanism behind the bone marrow-lung blood production is not yet known. “It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about,” said Guadalupe Ortiz-Muñoz, a postdoctoral researcher and the research’s co-author. But more research is sure to follow.
Now medical scientists and researchers can zero in on proving in human models that blood components — stem cells key among them — travel more freely than previously though, which could lead ultimately to advances in treatment options for various blood disorders.
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