Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bone marrow transplants may be improved due to the uncovering of a key mechanism

28.06.2002


Weizmann Institute scientists have uncovered a key mechanism that enables stem cells to exit the bone marrow into the blood circulation of healthy donors, as well as patients suffering from leukemia, other malignancies and blood disorders. Published in the current July issue of Nature Immunology, the findings may lead to more efficient clinical stem cell transplantations.



Bone marrow transplantation is a last-resort treatment that saves the lives of many patients with cancer and inherited blood disorders. In a transplantation, the patient’s malignant or defective stem cells in the marrow are destroyed, and healthy stem cells – either from a healthy donor or from the patient himself before or during treatment with chemotherapy – must be "encouraged" to come out of the marrow into the bloodstream (in other words, they must be "mobilized"). Thus, scientists have been trying to find out what triggers stem cell mobilization.

Dr. Tsvee Lapidot of Weizmann’s Immunology Department, and his PhD student, Isabelle Petit, found that the degradation of SDF-1, a key protein in the bone marrow, is crucial for stem cell mobilization. SDF-1 had previously been found by this and other research teams worldwide to anchor stem cells inside the marrow by activating adhesion molecules (molecules that serve as "glue"). Uncovered today is the "anchors aweigh" mechanism that frees stem cells into the blood.


The scientists investigated stimulation with the growth factor G-CSF, currently the most common clinical method used to induce stem cell mobilization. (In addition to its role in bone marrow transplantation, it is also used to treat children suffering from neutropenia, i.e. lack of white blood cells in the circulation). Before this study, G-CSF’s mode of action was largely unknown. Lapidot and Petit found that it reduces the number of SDF-1 proteins in the marrow by causing the production of degrading enzymes, in particular elastase. The result: stem cells attached to the marrow lose their "anchors" and flow into the bloodstream. Stem cells produced during SDF-1 degradation are not able to "cast anchor" to begin with and will also exit the marrow. The scientists found that stem cell mobilization peaked when SDF-1 levels in the bone marrow were at their lowest.

In addition, the team observed another of G-CSF’s effects: it causes an increase in the number of receptors of a certain type (called CXCR4) on stem cells and maturing white blood cells in the bone marrow. CXCR4 is the receptor that binds specifically with SDF-1. Surprisingly, they found that interactions between SDF-1 and CXCR4 are necessary for mobilization to take place. Inhibition of SDF-1 and CXCR4 interactions with neutralizing antibodies blocked stem cell mobilization.

The findings may lead to improved collection of stem cells for clinical transplantations. They also shed new light on neutropenia, resulting from a genetic defect in the elastase enzyme, which the group found plays a central role in degrading SDF-1.

An experimental system for human stem cells developed by Dr. Lapidot and his colleagues in 1999 enables the study of the mechanism by which human blood forming stem cells migrate from the blood into the bone marrow by transplanting human stem cells into immunodeficient mice, which lack the ability to reject foreign cells. In the current study this model was used to reveal the mechanism of human stem cell mobilization in these mice. Part of the study was also conducted with samples obtained from healthy donors treated with G-CSF for clinical stem cell transplantation.


###
The Weizmann Institute of Science in Rehovot, Israel is one of the world’s foremost centers of scientific research and graduate study. Its 2,500 scientists, students, technicians and engineers pursue basic research in the quest for knowledge and to enhance the quality of human life. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are high priorities at Weizmann.


Jeffrey J. Sussman | EurekAlert!

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

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: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Researchers release the brakes on the immune system

18.10.2017 | Health and Medicine

Separating methane and CO2 will become more efficient

18.10.2017 | Life Sciences

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>