Bodyguard macrophages protect stem cells from over-differentiation

Published on October 23, 2012 at 11:09 AM · No Comments

Hiding deep inside the bone marrow are special cells. They wait patiently for the hour of need, at which point these blood forming stem cells can proliferate and differentiate into billions of mature blood immune cells to help the body cope with infection, for example, or extra red blood cells for low oxygen levels at high altitudes. Even in emergencies, however, the body keeps to a long-term plan: It maintains a reserve of undifferentiated stem cells for future needs and crises. A research team headed by Prof. Tsvee Lapidot of the Institute's immunology Department recently discovered a new type of bodyguard that protects stem cells from over-differentiation. In a paper that appeared in Nature Immunology, they revealed how this rare, previously unknown sub-group of activated immune cells keeps the stem cells in the bone marrow "forever young."

Blood forming stem cells live in comfort in the bone marrow, surrounded by an entourage of support cells that cater to their needs and direct their development - the mesenchymal cells. But the research team, which included postdoctoral fellow Dr. Aya Ludin, Prof. Steffen Jung of the Immunology Department and his group, and Ziv Porat of the Biological Services Unit, discovered another type of support cell for the stem cells. These are an offshoot of the macrophage family, literally the "big eaters" of the immune system that are important, for instance, for bacterial clearance. The team found, however, that a rare sub-population of the bone-marrow macrophages has another role to play. Each of these rare macrophages can take a stem cell under its wing and prevent its differentiation.

Probing more deeply, the researchers revealed, in precise detail, how these macrophages guard the stem cells. They secrete substances called prostaglandins, which are absorbed by the stem cells. In a chain of biochemical events, these substances delay differentiation and preserve the youthful state of the stem cells. In addition, the prostaglandins work on the neighboring mesenchymal cells, activating the secretion of a delaying substance in them and increasing the production of receptors for this substance on the stem cells, themselves. This activity, says Lapidot, may help the non-dividing stem cells survive chemotherapy - a known phenomenon. Macrophages also live through the treatment, and they respond by increasing their prostaglandin output, thus heightening their vigilance in protecting the stem cells.

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