Most bone marrow transplants (BMT) accompanied by total body irradiation or strong chemotherapy treatment are aimed to kill a patient’s own hematopoietic stem cells (HSC), which are functionally abnormal, and to create free space (niches) in bone marrow for fresh and healthy donor HSC. On the other hand, radiation and chemotherapy could cause severe systemic side effects and simply make the patient very sick. So far we don’t know other methods for selective and efficient depletion of host HSC.
Even radiation and strong chemotherapy conditioning can’t avoid the problem of low level of engraftment (which has a direct correlation to chimerism in the recipient), which are essential for a successful BMT and the patient’s recovery. Now, it seems like there is a tool that helps to significantly increase engraftment of the donor’s hematopoetic stem cells after BMT. A recent study by Agnieszka Czechowicz from Irving Weissman’s group at Stanford University School of Medicine provides evidence that antibodies against HSC can more gently and selectively deplete host cells and clear niches, making them available for engraftment of donor cells.
The authors of the study used ACK2 (an antibody to common HSC surface marker c-kit) and showed that such treatment leads to transient removal of 98% of host’s HSC. After BMT, the chimerism of granulocytes in the mice treated by ACK2 was increased 10 times and achieved up to 90% donor cells.
Some interesting thoughs about this study:
– This kind of treatment provides us only a limited window for enhanced engraftment into available niches (amount of host’s HSC returned to nearly normal 23 days after administration).
– Donor’s chimerism after BMT in treated mice was linear (cell dose-dependent), meaning that treatment increased niche availability in bone marrow.
– Other antibody (2B8) to c-kit (but actually to the same isotype) only partially inhibit HSC compared with ACK2.
– The researchers don’t know whether or not this approach is going to work in humans, but at least they show it’s possible and I think this a great step forward, which could have a remarkable impact for BMT in clinic.
Study published in Science 23 November 2007: Vol. 318. no. 5854, pp. 1296 – 1299 DOI: 10.1126/science.1149726
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