Controlled mobilization of bone marrow progenitor cells

by Alexey Bersenev on March 24, 2009 · 0 comments

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The development of strategies to induce the release of stem cells and derivative progenitor cells from the bone marrow into the blood, a phenomenon termed mobilization, has focused almost exclusively on hematopoietic stem cells.
(Mikhail Kolonin and Paul Simmons)

Since the first attempts of mobilization of hematopoietic stem/progenitor cells (HSPC) from bone marrow to peripheral bloodstream in leukemia clinic in early 1980s, a lot of drugs and biologically active mediators were proposed for it. Some of them became real biotech blockbusters, some – on the way to market, some – still in experiments. But so far there were no sufficient and reproducible protocols discovered for mobilization of other cells than hematopoietic cells from bone marrow, such as endothelial progenitor cells (EPCs) and stromal mesenchymal progenitors (MSC). Now we got the first report, describing this possibility – Differential Mobilization of Subsets of Progenitor Cells from the Bone Marrow.

Authors used combination of drugs to differentially induce mobilization of HSPC or EPC or MSC. Their results are summarized by the picture:

some of conclusions and my thoughts below:

1. this is the first study with an attempt to clearly dissect mobilization of different bone marrow cell subsets;
2. defined combination of drug administration allows us to clearly dissect mobilization HSPC vs EPC, but not EPC vs MSC so far;
3. we still don’t know whether the same scheme is going to work in humans or not;
4. study is preclinical and can have significant impact in clinic, because safety of VEGF administration was demonstrated and different schemes of treatment were tested;
5. we still can not mobilize different hematopoietic progenitors, such as lymphoid, myeloid or megakaryocyte-erythroid, as distiguished from hematopoietic stem cells which are not cycling;
6. the mechanisms of EPC and MSC upon VEGF+AMD3100 administration remain unclear;
7. function of mobilized EPC and MSC should be investigated further;
8. other prospective agents to mobilize MSC should be widely tested, for example substance P;
9. in discussion authors supposed that disappointment of clinical trials used G-CSF for regeneration of heart muscle, could be explained by strict mobilization of HSPC only but not EPC or MSC which able to regenerate myocardium expectedly better.

finally i’d like to finish with a citation from the commentary, which unveils one of my favorite topics – “double-edged sword”:

In conclusion, this exciting study suggests that it may be possible to tailor the mobilization of individual populations to specific pathological conditions. However, it should be emphasized that the introduction of new mobilization regimes into the clinic must proceed with caution. In pathologies such as cancer—ironically the setting in which stem cell reconstitution is needed most—mobilization of progenitors could be a double-edged sword.

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