Sunday, 24 February 2013

Bone marrow contains distinct stem cell niches

In a recent study, researchers from the Washington University School of Medicine present, for the first time, the existence of more than one stem cell niches in bone marrow tissue. Their findings have the potential to improve the effects of chemotherapy and accelerate the recovery followed after a hematopoietic stem cell transplantation.

During the experiments, the scientists conditionally deleted a critical gene (CXCL12) in a group of mice, from candidate niche cells in the bone marrow and assessed the effects on hematopoietic stem cells (HSCs). CXCL12 is a key-component that keeps HSCs healthy. Eventually, they discovered that each stem cell niche holds only certain blood stem cells that are nourished by a unique set of support cells.

The study strongly indicates that there is not only one stem cell niche in the bone marrow but instead there is one niche for stem cells destined to become blood cells and another one for stem cells destined to become cells of the immune system (e.g. lymphocytes like B-cells and T-cells).

Image of a human lymphocyte
Picture of a human lymphocyte

According to the researchers, the findings are very important as they indicate that it may be possible to selectively intervene to different stem cell populations belonging to different bone marrow stem cell niches. For example, one theoretical application would be a drug that encourages transplanted hematopoietic stem cells to establish themselves faster and more efficiently to their new environment. Essentially, this would result in a faster recovery for people who have received a HSC transplant.

A second application would be a drug that can alter the niche where cancer cells hide, pushing them into the bloodstream. There, their ability to withstand the effects of chemotherapy would be greatly reduced.

Hematopoietic stem cell transplant

Daniel Link, senior author of the study said:

“Our results offer hope for targeting these niches to treat specific cancers or to improve the success of stem cell transplants. Already, we and others are leading clinical trials to evaluate whether it is possible to disrupt these niches in patients with leukaemia or multiple myeloma.” 

As mentioned before, the study strongly indicates that disruption to these niches could potentially increase the effects of chemotherapy. A phase II pilot study, led by oncologist Geoffrey Uy, is currently running with the purpose to examine if a specific drug, G-CSF, has this exact property. The trial will enrol patients with lymphoblastic leukaemia that has either recurred or is resistant to treatment and will be carried out in the Siteman Cancer Center. The drug is already approved by the FDA and is used in certain cancer patients to accelerate recovery after chemotherapy, by stimulating the production of new white blood cells.

However, in this clinical trial the drug will be given 5 days prior to receiving the chemotherapy and not after, as the standard protocol is. Hopefully, G-CSF does have the capacity to disrupt the protective environment of the bone marrow niche where cancer cells hide, making them more vulnerable to the chemotherapy that will follow.

“Next, we hope to understand how stem cell niches can be manipulated to help patients undergoing stem cell transplants.” said Link.

Reference
Greenbaum, A., Hsu, Y., Day, R., Schuettpelz, L., Christopher, M., Borgerding, J., Nagasawa, T., & Link, D. (2013). CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance Nature DOI: 10.1038/nature11926

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