Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Distinct niches in bone marrow nurture blood stem cells

25.02.2013
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:
http://www.wustl.edu

More articles from Health and Medicine:

nachricht Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

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: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>