Insights into rare immune cells that keep blood stem cells in a youthful state may lead to better treatments

October 22, 2012
Insights into rare immune cells that keep blood stem cells in a youthful state may lead to better treatments
Prostaglandins guard stem cells by increasing the production of an inhibitory factor in the mesenchymal bone marrow cells. Mesenchymal cells are marked with a green protein (left); the inhibitory factor is red (center). Combined image (right): Treatment with prostaglandins (bottom) increases the secretion of the inhibitory factor

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 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 , 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 , 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.

The 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 resist the urge to differentiate.

In previous work in Lapidot's lab, it was discovered that prostaglandin treatments can improve the number and quality of stem cells. This insight is currently being tested by doctors in clinical transplantation trials for the use of stem cells from umbilical cord blood to treat adult leukemia patients. These trials are showing that prior treatment with prostaglandins improves migration and repopulation potential, enabling the small quantities of cord blood stem cells to better cure the patients. "The present study hints at the possibility of further increasing the support for bone marrow stem cells by exploring this intriguing connection between the and ," says Lapidot. "An understanding of the mechanisms at work in these cells might improve the success of stem cell transplantation, especially that of umbilical blood."

Explore further: Researchers find way to help donor adult blood stem cells overcome transplant rejection

More information: www.nature.com/ni/journal/vaop … nt/full/ni.2408.html

Related Stories

Researchers find way to help donor adult blood stem cells overcome transplant rejection

August 4, 2011
Findings by UT Southwestern Medical Center researchers may suggest new strategies for successful donor adult stem cell transplants in patients with blood cancers such as leukemia, lymphoma and myeloma.

Recommended for you

Antibody protects against Zika and dengue, mouse study shows

September 25, 2017
Brazil and other areas hardest hit by the Zika virus - which can cause babies to be born with abnormally small heads - are also home to dengue virus, which is spread by the same mosquito species.

Gene immunotherapy protects against multiple sclerosis in mice

September 21, 2017
A potent and long-lasting gene immunotherapy approach prevents and reverses symptoms of multiple sclerosis in mice, according to a study published September 21st in the journal Molecular Therapy. Multiple sclerosis is an ...

New academic study reveals true extent of the link between hard water and eczema

September 21, 2017
Hard water damages our protective skin barrier and could contribute to the development of eczema, a new study has shown.

Exposure to pet and pest allergens during infancy linked to reduced asthma risk

September 19, 2017
Children exposed to high indoor levels of pet or pest allergens during infancy have a lower risk of developing asthma by 7 years of age, new research supported by the National Institutes of Health reveals. The findings, published ...

Cholesterol-like molecules switch off the engine in cancer-targeting 'Natural Killer' cells

September 18, 2017
Scientists have just discovered how the engine that powers cancer-killing cells functions. Crucially, their research also highlights how that engine is fuelled and that cholesterol-like molecules, called oxysterols, act as ...

MicroRNA helps cancer evade immune system

September 18, 2017
The immune system automatically destroys dysfunctional cells such as cancer cells, but cancerous tumors often survive nonetheless. A new study by Salk scientists shows one method by which fast-growing tumors evade anti-tumor ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.