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 Spread of deadly eye cancer halted in cells and animals
13.11.2018 | Johns Hopkins Medicine

nachricht Breakthrough in understanding how deadly pneumococcus avoids immune defenses
13.11.2018 | University of Liverpool

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: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

How algae and carbon fibers could sustainably reduce the athmospheric carbon dioxide concentration

14.11.2018 | Life Sciences

NIH scientists illuminate causes of hepatitis b virus-associated acute liver failure

14.11.2018 | Life Sciences

The unintended consequences of dams and reservoirs

14.11.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>