Weizmann Institute scientists have revealed a mechanism responsible for the mobility of stem cells in humans. The discovery may lead to an improvement in the efficiency of bone marrow transplants
Prof. Zvi Lapidot and research student Isabel Petit. Migratory cells
Weizmann Institute scientists have discovered a key mechanism that allows stem cells to leave the bone marrow and enter the bloodstream of healthy blood donors. The mechanism also works in the body of patients with leukemia, other blood diseases, and some types of cancer. These findings, published in the July issue of the scientific journal Nature Immunology, may lead to the development of more effective ways to transplant stem cells contained in the bone marrow.
Transplantation of stem cells from the bone marrow is a complex process, which is usually performed only when there is no other option left. During the transplantation process, the damaged stem cells are destroyed (through pre-irradiation), and in their place, other, normal stem cells are introduced into the bloodstream. In order to obtain the healthy stem cells necessary for transplantation (either from a healthy blood donor or from the patient himself before and during chemotherapy), they need to be "encouraged" to leave the bone marrow and enter the bloodstream. In other words, the requested cells need to become mobile, so that they can reach the place where the researchers and doctors can collect them and prepare them for transplantation. But how can the stem cells become mobile?
Prof. Zvi Lapidot, and research student Isabel Pettit from the Department of Immunology of the Weizmann Institute of Science, found that the breakdown of a certain protein (SDF-1) found in the bone marrow is essential for the process of imparting the mobility feature to the stem cells from the bone marrow to the bloodstream. It was already known in the past that this protein serves as a kind of "anchor" that engages the stem cells to their place inside the bone marrow (using a certain "glue" molecule).
The current research of Prof. Lapidot and Isabelle Petit shows how the stem cells "raise an anchor" and start their journey into the bloodstream.
Top: the control group that was not treated with G-CSF. The SDF-1 protein is colored red. Bottom: the group treated with G-CSF. Little presence of the protein SDF-1
To stimulate the mobility feature in the stem cells, the scientists used a growth factor called G-CSF. This substance is used to impart mobility to stem cells in various medical processes, but until the current research of Prof. Lapidot and Isabelle Petit, it was not clear how exactly it works. Prof. Lapidot and Isabel Pettit found in their research that this growth factor reduces the amount of SDF-1 in the bone skeleton, thereby causing the stem cells to "raise anchor" and embark on a journey into the bloodstream. To do this, the G-CSF induces the formation of disintegrating enzymes, especially the enzyme elastase.
These enzymes are the ones that break down the SDF-1 proteins that serve as the "anchor" of the stem cells. In this study, the scientists learned that the growth factor G-CSF also causes an increase in the amount of CXCR4 receptors on the surface of the stem cells and maturing white blood cells in the bone marrow. CXCR4 receptors interact uniquely with SDF-1 proteins and the scientists discovered that this interaction also plays an important role in imparting the mobility feature to the stem cells.
These findings may lead to the development of more efficient ways to collect stem cells necessary for transplants. In addition, they may help in understanding the molecular mechanisms involved in the disease of neutropenia, which results from a genetic defect in the enzyme elastase (the same enzyme that plays an important role in breaking down the protein, SDF-1, which functions as an "anchor" of the stem cells).
In this study, an experimental system developed by Prof. Lapidot and his colleagues was used in the past. This system makes it possible to examine the migration mechanism of human stem cells from the blood to the bone marrow through the transplantation of human stem cells in mice whose bodies lack the immune system (and therefore they do not reject the foreign stem cells). Another part of the study was carried out with human cells taken from healthy blood donors treated with SDF-1 with the aim of collecting stem cells from blood, and transplanting them into patients who needed it.
Average level of the SDF-1 protein in the control group compared to a group treated with G-CSF after 24 hours
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hello kafir,
These days I am working on a seminar on the above topic.
I would love to receive more information (if possible) about the study.
Thanks in advance
svetlanaga@gmail.com
Also, if you are able to help prepare a follow-up notice, rather.
hello kafir
The Weizmann Institute uploaded a lot of articles to their website and I also took the current article from there, and I assume that this is the update of the archive, but they mostly did not specify the date of the original article.
I will try to talk to the speaker's office tomorrow and we will see how the articles are uploaded and, nevertheless, updated from when the article was, and if anything has been updated.
Please correct: the above study was published in 2002 and is therefore not innovative.
Since then, many studies have been published regarding the mechanism behind the mobilization of stem cells from the bone marrow into the circulation through the administration of G-CSF. Among other things: activity of various proteolytic enzymes that break down the SDF-1 protein, a decrease in the number of cells that secrete SDF-1 (=bone-building cells), activity of bone-dissolving cells that damage the "niche" where the stem cells are kept and thus actually release them.
Since I am a PhD student belonging to this group, if any of you have questions, I will be happy to answer.