Bone Cells that Influence Blood Stem Cell Replication and Migration

Related News: Stem Cell Research

Osteoblasts, cells responsible for bone formation, have been found by researchers at the Joslin Diabetes Center to be directly involved in the proliferation and expansion of blood-forming hematopoietic stem cells.

The finding improves understanding of how such stem cells work and could have implications for the future of bone marrow and peripheral blood progenitor cell transplants, which are used in the treatment of a variety of illnesses – including leukemia, lymphoma and immunodeficiency.

According to lead author Amy J. Wagers, Ph.D., Principal Investigator in the Joslin Section on Developmental and Stem Cell Biology - in normal individuals, blood-forming stem cells continually seed the production of all cells in the adult blood system.

Appropriate regulation of stem cell activity is essential for maintaining this normal cell replacement, and for supporting repair of the blood system after injury. Earlier studies implicated bone-lining osteoblasts as specialized cells in the bone marrow environment that communicate physiologically relevant signals to stem cells. But these studies were complicated by the presence of other cell types within the bone marrow. As a result, whether osteoblasts in particular could modulate blood-forming stem cell activity remained controversial.

To clarify this issue, Wagers and co-author Shane R. Mayack, Ph.D., Research Fellow in the Joslin Section on Development and Stem Cell Biology, developed a strategy to isolate osteoblasts and then exposed these osteoblasts to bone marrow stem and progenitor cells in vitro to test their ability to alter stem cell proliferation and function.

How it was done:
- the researchers took osteoblasts from normal mice and from mice treated with drugs designed to cause stem cells to proliferate and migrate
- then exposed the isolated osteoblasts to bone marrow progenitor cells from normal mice in vitro
- bone marrow cells exposed to the osteoblasts taken from the treated mice proliferated rapidly, while those from untreated mice were inhibited from replicating
According to Wagers, this effect demonstrates that the osteoblast cells are capable of communicating to the stem cells the physiological signals provided by the drugs. 'It demonstrates that osteoblasts act as functional niche cells capable of directly regulating stem cell activity,' she said.

The new finding also provides an opportunity to study potential changes in niche cells that may contribute to diseases such as leukemia or bone marrow failure.

The work was supported in part by grants from the Smith Family Medical Foundation, Paul F. Glenn Laboratories, a Burroughs Wellcome Fund Career Award and the National Institutes of Health.

About Joslin Diabetes Center
Joslin Diabetes Center is the world’s largest diabetes clinic, diabetes research center and provider of diabetes education. Joslin is dedicated to ensuring people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure for the disease. Founded in 1898 by Elliott P. Joslin, M.D., Joslin is an independent nonprofit institution affiliated with Harvard Medical School. For more information on Joslin, call 1-800-JOSLIN-1 or visit http://www.joslin.org.



Posted on May 22, 2008 02:50 PM

 
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