Astonishing research out this week from the journal
Nature shows that the lungs are a major site of platelet production (the proto-cells that allow for blood clotting), producing about 50% of the platelets circulating in the blood stream in mice. Furthermore, and this is the mind-blowing part for those who study physiology, it turns out that the lungs produce a previously unknown reservoir of blood stem cells capable of restoring blood production when the stem cells of the bone marrow are depleted. As of a few weeks ago, the red bone marrow was believed to be the principal site of blood cell production.
This new research was made possible by two innovative experiments, detailed in
this article:
The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:
First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.
“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-MuÒoz, PhD, also a postdoctoral researcher in the Looney lab and the paper’s other co-first author. “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.”
In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation ó much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.
Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.
“To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” said Looney, who is also an attending physician on UCSF’s pulmonary consult service and intensive care units.
Needless to say, this research has tremendous implications in the treatment of blood cell and platelet disorders, and also may shed some light on the potential complications that can result from lung transplantation. This overturning of several decades of accepted knowledge shows how science continues to advance as new techniques come to light, though it is important to note that this research has yet to be confirmed on human test subjects. Hopefully this new research will serve us well in leading to new medical techniques to help those with blood cell disorders.
Now it is time for me to inform my students that chapter 19 of their textbook might be partially out of date...
