Cincinnati researchers observe the birth of blood cells in mice; find surprising results

CINCINNATI, Ohio — The cells of the blood that carry oxygen throughout the circulatory system, and those that form our immune system may be different, but they all come from the same place: our bone marrow.

It’s well-known that the bone marrow generates new blood cells, but it’s a process no one has been able to observe in fine detail — until now. Researchers in Cincinnati recently found a way to peer into bones of mice and watch new blood cells being born and maturing, revealing important information that may one day help improve the treatment of various blood-borne disorders.

Depending on the specific cell type, the lifespan of a blood cell ranges anywhere from a few days to a few months. Platelets for example live eight to 10 days, eosinophils — a type of white blood cells — roughly three weeks, and the red blood cells that carry oxygen to the tissues of the body survive for around four months.

After they have completed their lifespan, blood cells are removed from the bloodstream by the spleen.

Meanwhile, deep inside the bones, an army of replacements are continuously being birthed and their fates determined, and a team of scientists led by experts at Cincinnati Children’s Hospital has found a way to watch it all happen inside a living mouse.

The scientists were able to count the different types of blood cells being formed inside the tiny bones of a mouse and pinpoint the strings and clusters of cells within the bone marrow that are responsible for producing specific types of blood cells.

Their research, published in March in the journal Nature, has added a new understanding of the anatomy of bone marrow was well as a new picture of how the skeleton responds to stresses such as infection or blood loss.

One big surprise? Not all bones respond the same way.

“Stunningly, we found that the response to hematopoietic insults varies across the skeleton. We speculate that certain bones have specialized to preferentially respond to some insults, and this will be the focus of future studies,” the authors stated.

The discovery that different cell types are formed at specific sites within the bone marrow raises new challenges and opportunities for diagnosing and treating a number of blood-related conditions, the authors said.

“For example, our data shows that biopsies that draw marrow from just one type of bone may not provide a full picture of how the blood production system has been affected by a disease or other insult,” said Daniel Lucas, one of the study’s authors and a researcher in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children’s.

“Meanwhile, efforts to stimulate production of certain blood cell types may be dramatically improved by focusing on specific bone types.”

For example, the researchers found that blood loss triggered rapid red blood cell production in the sternum, tibia, vertebrae, and humerus -- but not in the skull. Blood loss also temporarily reduced the number of B cells, the white blood cells that produce antibodies, that are produced across the skeleton.

“These variations are important because until now, mouse studies of blood cell biology have depended almost entirely upon material collected from the femur and tibia,” Lucas says.

Researchers also observed how clusters of cells form within the marrow to act as blood cell production factories, and that the microenvironments that surround the new cells as they mature significantly influences which cell types they become — oxygen-carrying red blood cells versus infection-fighting white blood cells, for example.

Much more research will be needed to fully understand how different parts of the skeleton become specialized producers of specific blood components, said Lucas. Also, studies will be needed to confirm how much of the bone marrow stress response observed in mice also occurs in humans.

However, a better, more nuanced understanding of blood cell production may one day improve the effectiveness of treatments that support healthy blood cell production he said.

“It might even allow to build artificial bones capable of producing red blood cells for transfusion.”