Stem Cell Bodyguards
A subpopulation of macrophages supports the youth of hematopoietic stem cells
LifeSciencesToday based on the materials of the Weizmann Institute of Science: Stem Cell BodyguardsDeep in the bone marrow, hematopoietic stem cells that are very necessary for our body "hide".
They are patiently waiting for the hour when they can begin to proliferate and differentiate, for example, into billions of mature cells of the immune system to help the body cope with infection, or into red blood cells at low oxygen levels at high altitudes. But even in such emergencies, the body follows a long-term plan: it reserves undifferentiated stem cells for future needs and in case of a crisis.
A group led by Tsvee Lapidot, Professor of the Department of Immunology at the Weizmann Research Institute, has just discovered a new type of cells that prevent untimely differentiation of stem cells. In an article published in the journal Nature Immunology (Ludin et al., Monocytes-macrophages that express alpha-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow), Lapidot and his colleagues describe how this rare and previously unknown subgroup of activated immune cells supports the "eternally young" state of bone marrow stem cells.
Hematopoietic stem cells live in the bone marrow in complete comfort, surrounded by a retinue of supportive – mesenchymal – cells that serve their needs and guide their development. A new type of stem–supporting cells discovered by Israeli scientists are representatives of the lateral branch of the macrophage immune system cell family (literally, "big eaters"), which perform an important function of removing pathogenic bacteria from the body. However, this rare subpopulation of bone marrow macrophages plays a different role. Each of these macrophages can take a stem cell under its wing and prevent its differentiation.
Scientists managed to find out in detail exactly how these macrophages protect stem cells. They are characterized by high expression of the enzyme cyclooxygenase COX-2 (cyclooxygenase COX-2), a catalyst for the first stage of prostaglandin synthesis. As a result of a chain of biochemical events, these substances ultimately delay the differentiation of stem cells: prostaglandins, in this case PGE2, are absorbed by stem and progenitor cells located near macrophages and prevents their depletion, limiting the formation of reactive oxygen species by suppressing the activity of Akt kinase; in addition, prostaglandins affect neighboring mesenchymal cells, activating secretion they are another substance that delays differentiation (chemokine CXCL12), and stimulate the formation of receptors of this substance on stem cells.
Prostaglandins "protect" hematopoietic stem cells by enhancing the synthesis of inhibitory factor by mesenchymal bone marrow cells. Mesenchymal cells are labeled with a green protein (left); the inhibitory factor is red. Combined image (right): prostaglandin treatment (bottom) enhances the secretion of an inhibitory factor. (Photo: Weizmann Institute of Science)
According to Professor Lapidot, this function can help non–dividing stem cells survive chemotherapy - a well-known phenomenon. Macrophages also experience its effects and respond to this stress by increasing the release of prostaglandins, thus showing increased vigilance in protecting stem cells.
Macrophages-bodyguards increase their activity in case of infection. While other members of the macrophage family are engaged in fighting pathogens, their relatives in the bone marrow are working hard to ensure that the stem cell pool does not succumb to the temptation to differentiate.
In the previous work of Professor Lapidot's laboratory, it was found that prostaglandin treatment can increase the number and improve the quality of stem cells. This fact is currently being verified by doctors during clinical trials of cord blood stem cell transplantation as a method of treating leukemia. The first data obtained confirm that the preliminary administration of prostaglandins enhances their migration and repopulation potential, allowing for higher results.
"Studying the intriguing connection between immune and stem cells may allow us to strengthen support for bone marrow stem cells," Lapidot suggests. "Understanding the mechanisms that work in these cells can improve the efficiency of stem cell transplantation, in particular, cord blood cells."
Portal "Eternal youth" http://vechnayamolodost.ru29.10.2012