Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Distinct niches in bone marrow nurture blood stem cells

In research that could one day improve the success of stem cell transplants and chemotherapy, scientists have found that distinct niches exist in bone marrow to nurture different types of blood stem cells.

Stem cells in the blood are the precursors to infection-fighting white blood cells and oxygen-carrying red blood cells.

Distinct niches exist in bone marrow to nurture different types of blood stem cells, new research shows. In mice bone marrow, blood stem cells, highlighted in blue, are nurtured by support cells shown in red and yellow.

Credit: Daniel Link, M.D.

The research, by a team at Washington University School of Medicine in St. Louis, is reported Feb. 24 in the advance online edition of Nature.

The new findings, in mice, suggest that it may be possible to therapeutically target support cells in a particular niche. On the one hand, a drug that nourishes support cells could encourage blood stem cells to establish themselves in the bone marrow, enabling patients who have had stem cell transplants to more quickly rebuild their immune systems.

On the other, tumor cells are known to hide in the bone marrow, and a drug that disrupts the niche environment may drive cancer cells into the bloodstream, where they are more vulnerable to the damaging effects of chemotherapy.

"Our results offer hope for targeting these niches to treat specific cancers or to improve the success of stem cell transplants," says senior author Daniel Link, MD, the Alan A. and Edith L. Wolff Professor of Medicine. "Already, we and others are leading clinical trials to evaluate whether it is possible to disrupt these niches in patients with leukemia or multiple myeloma."

Working in the mice, the researchers selectively deleted a critical gene, CXCL12, which is known to be important for keeping blood stem cells healthy. Rather than knock out the gene in all of the support cells in a niche, the researchers deleted the gene in specific types of support cells. This led to the discovery that each niche holds only certain blood stem cells that are nourished by a unique set of support cells.

"What we found was rather surprising," Link says. "There's not just one niche for developing blood cells in the bone marrow. There's a distinct niche for stem cells, which have the ability to become any blood cell in the body, and a separate niche for infection-fighting blood cells that are destined to become T cells and B cells."

The findings provide a strong foundation for investigating whether disrupting these niches can improve the effectiveness of chemotherapy.

In a phase II pilot study led by Washington University medical oncologist Geoffrey Uy, MD, assistant professor of medicine, Link is evaluating whether the drug G-CSF can alter the stem cell niche in patients with acute lymphoblastic leukemia whose cancer has recurred or is resistant to treatment. The drug was approved by the Food and Drug Administration more than 20 years ago to stimulate production of white blood cells in patients undergoing chemotherapy, who often have weakened immune systems and are prone to infections.

But Uy and colleagues will evaluate the drug when it is given before chemotherapy. Patients enrolled in the trial at the Siteman Cancer Center will receive G-CSF for five days before chemotherapy, and the investigators will determine whether it can disrupt the protective environment of the bone marrow niche and make cancer cells more sensitive to chemotherapy.

While it's too early to know whether the treatment approach will be successful, Link's new research in mice is bolstered by a companion paper in the same issue of Nature. In that research, Sean Morrison, PhD, director of the Children's Medical Center Research Institute at the University of Texas Southwestern Medical Center in Dallas, used similar molecular methods to also discover distinct niches in the bone marrow for blood stem cells.

"There's a lot of interest right now in trying to understand these niches," Link adds. "Both of these studies add new information that will be important as we move forward. Next, we hope to understand how stem cell niches can be manipulated to help patients undergoing stem cell transplants."

The research is supported by the National Institutes of Health (grants RO1 HL60772 and F30 HL097423)

Greenbaum A, Hsu Y-MS, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, Nagasawa T, Link DC. CXCL12 production by early mesenchymal progenitors is required for haemoatopoietic stem-cell maintenance. Nature. Advance online publication Feb. 24, 2013.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Caroline Arbanas | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht UofL scientists identify critical pathway to improve muscle repair
01.12.2015 | University of Louisville

nachricht University of California Scientists Create Malaria-Blocking Mosquitoes
30.11.2015 | University of California, Irvine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: How do Landslides control the weathering of rocks?

Chemical weathering in mountains depends on the process of erosion.

Chemical weathering of rocks over geological time scales is an important control on the stability of the climate. This weathering is, in turn, highly dependent...

Im Focus: How Cells in the Developing Ear ‘Practice’ Hearing

Before the fluid of the middle ear drains and sound waves penetrate for the first time, the inner ear cells of newborn rodents practice for their big debut. Researchers at Johns Hopkins report they have figured out the molecular chain of events that enables the cells to make “sounds” on their own, essentially “practicing” their ability to process sounds in the world around them.

The researchers, who describe their experiments in the Dec. 3 edition of the journal Cell, show how hair cells in the inner ear can be activated in the absence...

Im Focus: Climate study finds evidence of global shift in the 1980s

Planet Earth experienced a global climate shift in the late 1980s on an unprecedented scale, fuelled by anthropogenic warming and a volcanic eruption, according to new research published this week.

Scientists say that a major step change, or ‘regime shift’, in the Earth’s biophysical systems, from the upper atmosphere to the depths of the ocean and from...

Im Focus: Innovative Photovoltaics – from the Lab to the Façade

Fraunhofer ISE Demonstrates New Cell and Module Technologies on its Outer Building Façade

The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...

Im Focus: Lactate for Brain Energy

Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.

In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...

All Focus news of the innovation-report >>>



Event News

European Geosciences Union meeting: Media registration now open (EGU 2016 media advisory 1)

01.12.2015 | Event News

Urbanisation and migration from rural areas challenging agriculture in Eastern Europe

30.11.2015 | Event News

Fraunhofer’s Urban Futures Conference: 2 days in the city of the future

25.11.2015 | Event News

Latest News

USGS projects large loss of Alaska permafrost by 2100

01.12.2015 | Earth Sciences

New study reveals what's behind a tarantula's blue hue

01.12.2015 | Life Sciences

Climate Can Grind Mountains Faster Than They Can Be Rebuilt

01.12.2015 | Earth Sciences

More VideoLinks >>>