Key Bone Marrow cells Hide at Edges, Study Finds

By Maggie Fox, Health and Science Correspondent

WASHINGTON — Scientists have found blood stem cells hiding out in the edges of bone marrow, and said on Monday their finding could help ease lifesaving stem cell transplants for diseases such as cancer.

They invented a technique that makes it possible to see a stem cell alive in bone marrow — something never done before.

Scientists usually find the powerful but elusive cells by looking for proteins called markers that are active on the stem cells’ surfaces.

The cells are not clustered throughout bone marrow, as had been thought, but live alongside bone-forming cells on the edges of the marrow, the team at the University of Michigan Medical School and University of Tsukuba in Japan wrote in the Proceedings of the National Academy of Sciences.

This might make transplants easier, said Dr. Doug Engel, who worked on the study. Currently doctors must remove large amounts of bone marrow from a donor and separate stem cells, which are infused into a sick patient.

"Maybe we can find a way to expand the stem cell population in the niche," Engel said in a telephone interview.

"Then perhaps we can make human bone marrow harvests less invasive and less painful."

Where the stem cells live might hold a key to their abilities to create all the different types of blood cells, Engel said.

FLUORESCENT GENE

To find the stem cells, Norio Suzuki and colleagues at the University of Tsukuba spliced a green fluorescent protein gene from jellyfish into two genes uniquely used by the blood stem cells, one called Gata-2, and a gene called IS that helps control Gata-2.

This made the stem cells glow under ultraviolet light. "We made a whole mouse that would express green fluorescent protein under the control of the Gata-2 gene promotor," Engel said.

"We took time-lapse movies of frozen sections from mouse leg bone as seen under a fluorescent microscope," Engel added.

"They clearly show individual, isolated hematopoietic stem cells at the edge of the bone marrow."

When bone marrow stem cells, called hematopoietic stem cells, are transplanted, they proliferate, giving rise to immune cells and various other blood cells.

Scientists had presumed they circulated throughout the bone marrow. In fact, they sat still and in contact with osteoblasts — bone-forming cells.

In a second study in the same journal, another team of scientists said they found another unusual source of support for stem cells — prion proteins.

Prions are perhaps best known as the agents that, when misshapen, cause mad cow disease and related diseases. Mad cow disease, known scientifically as bovine spongiform encephalopathy, and similar diseases destroy the brains of other animals and humans.

Prions have a normal function too — but nobody knows what it is.

Susan Lindquist of the Massachusetts Institute of Technology and colleagues found prion protein expressed, or active, in bone marrow stem cells. She said that means prions probably help blood stem cells during the transplant process and might serve as a marker to help find them.