Stem cells in the bone marrow
Renovators, who deal with the maintenance of buildings, are known as those who work simultaneously on several jobs at the same time. Now it turns out that certain cells that deal with maintenance are also characterized by the same feature. A team of scientists from the Weizmann Institute of Science, led by Prof. Zvi Lapidot from the Department of Immunology, discovered that immune cells involved in the maintenance of bone tissue also play a central role in the renewal of the blood system as part of the body's immune and rehabilitation mechanisms. This discovery, which may lead, in the future, to innovations in bone marrow transplantation techniques, and also to a better understanding of blood and bone diseases, is being published these days in the scientific journal Nature Medicine.
All blood cells, including various types of immune cells, are formed in the internal cavity of the bone, where the bone marrow is located and functions. Among the various cells that make up the bone marrow are also blood-forming stem cells ("hematopoietic"), which are capable of multiplying and creating the different types of blood cells. These blood cells work in a kind of special niches that serve as a kind of "nurseries" located on the inner wall of the bone. Within these isolated "nurseries", and with the help of various supporting cells, the stem cells remain in their initial state and do not differentiate. Only when they leave the "nurseries" and enter the bloodstream, the stem cells become mature blood cells and are even able to migrate to distant organs where damage has occurred to help in their rehabilitation.
Other cells also work on the inner wall of the bone: osteoblasts, which are involved in building bone, and osteoclasts, which are involved in breaking down bone tissue. These joint cells, which are giant cells with many nuclei, are created when stem cells of the immune system differentiate and unite, as a result of a special signal they receive from the bone-forming cells (the osteoblasts). This is how regulation is carried out and a balance is created between the action of breaking down the bone tissue and building it, which ensures the bone's strength and health.
Prof. Lapidot, together with Dr. Orit Kolt and other members of his research group, discovered that the cells from the bone joints, the osteoclasts, play an important role in releasing the stem cells from the bone marrow into the blood vessels. It turns out that while these cells are busy breaking down the bone tissue, they allow stem cells to leave the closed "nurseries" into the bloodstream. Although a certain amount of stem cells is always in the bloodstream, when bleeding or other distress occurs in the body as a result of inflammation, there is a "call to recruit" more cells as part of the defense and restoration mechanisms. The scientists of the institute discovered that this "call for recruitment" is expressed in the increased production of the cells from the bone joints, the osteoclasts. These cells create holes in the bone tissue and thereby release more stem cells into the bloodstream. In addition to this, they also break down substances that attract the stem cells to the bone marrow and help them remain in their initial, pre-differentiated state.
This research was carried out in mice, including mice of a special strain developed in the laboratory of Prof. Ari Elson in the department of molecular genetics of the cell at the Weizmann Institute of Science. In the body of young females of this species, the cells of the bone joints do not function properly. The scientists found that in these females the level of stem cells in the blood was particularly low. In another experiment, carried out in normal mice, the scientists were able to stimulate the production of cells from the bone joints by using the same signaling substance used by the bone-building cells. As a result, an increased release of stem cells into the bloodstream was observed, an essential step in increasing the activity of the immune system in order to repair malfunctions in the body.
This discovery may help increase the amount of stem cells in the blood of bone marrow donors. In addition, it may help to better understand the processes of bone breakdown and renewal, which may help in the development of new ways to treat osteoporosis, as well as autoimmune diseases that damage the bone and malignant tumors that metastasize to the bone.
