Stem Cell Bodyguards
Hiding deep inside the bone marrow are special cells that wait patiently for the hour of need. At that point, these blood-forming stem cells can proliferate and differentiate into billions of mature blood immune cells to help the body cope with infection, or extra red blood cells needed 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 postdoctoral fellow
Dr. Aya Ludin, Prof. Steffen Jung, Immunology
Department and his group, and Ziv Porat of the
Biological Services Unit discovered another type of support cell for the stem cells.
These cells are an offshoot of the macrophage family
literally the “big eaters” of the immune system
that are important, for instance, for eating up bacteria.
The team found that a rare sub-population of the
bone-marrow macrophages can take a stem cell
under wing and prevent differentiation.
Probing deeply, researchers revealed in precise detail how
these macrophages guard stem cells. These bone-marrow
macrophages secrete substances called prostaglandins,
which are absorbed by the stem cells. In a chain of
biochemical events, the prostaglandins delay differentiation
and preserve the youthful state of the stem cells.
Additionally, prostaglandins activate neighboring
mesenchymal cells to secrete a delaying substance
which increases the formation of receptors for this
delaying substance on the surface of the stem cells.
Lapidot believes this activity may help non-dividing
stem cells survive chemotherapy a known phenomenon.
Macrophages also live through chemotherapy and respond
by increasing their own prostaglandin output, thus
heightening their protection of the stem cells.
Bodyguard macrophages also increase their activity in times of infection. While other members of the macrophage family are recruited to fight the pathogens, their 'cousins' in the bone marrow are hard at work ensuring that a pool of stem cells will be blocked from differentiation.
In previous work by Lapidot’s lab, it was obsevered that prostaglandin treatments can improve the number and quality of stem cells. An observation that is currently being tested by doctors in clinical trials using umbilical cord blood stem cells to treat adult leukemia patients. These trials are showing that prior treatment with prostaglandins improves migration and repopulation potential of stem cells, enabling the small quantities of cord blood stem cells introduced to proliferate and better assist patients.
Lapidot: “The present study hints at the possibility of further increasing the support for bone marrow stem cells by exploring this intriguing connection between the immune cells and stem cells. An understanding of the mechanisms at work in these cells might improve the success of stem cell transplantation, especially that of umbilical blood.”
Prof. Steffen Jung’s research is supported by the Leir Charitable Foundations; the Leona M. and Harry B. Helmsley Charitable Trust; the estate of Olga Klein Astrachan; the estate of Lola Asseof; Lord David Alliance, CBE; and the Adelis Foundation.
Prof. Tsvee Lapidot’s research is supported by the Leona M. and Harry B. Helmsley Charitable Trust. Prof. Lapidot is the incumbent of the Edith Arnoff Stein Professorial Chair in Stem Cell Research.
Original article: http://wis-wander.weizmann.ac.il/stem-cell-bodyguards