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 Diabetes mellitus: A risk factor for early colorectal cancer
27.05.2020 | Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

nachricht Ultra-thin fibres designed to protect nerves after brain surgery
27.05.2020 | Martin-Luther-Universität Halle-Wittenberg

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: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

Black nitrogen: Bayreuth researchers discover new high-pressure material and solve a puzzle of the periodic table

29.05.2020 | Materials Sciences

Argonne researchers create active material out of microscopic spinning particles

29.05.2020 | Materials Sciences

Smart windows that self-illuminate on rainy days

29.05.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>