Research ArticleBone Marrow Transplantation

Diabetes Impairs Hematopoietic Stem Cell Mobilization by Altering Niche Function

Science Translational Medicine  12 Oct 2011:
Vol. 3, Issue 104, pp. 104ra101
DOI: 10.1126/scitranslmed.3002191

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Boosting Stem Cell Mobilization

Transplantation of hematopoietic stem cells (HSCs) from the bone marrow is a successful approach for treating blood diseases and certain cancers. Usually, the patient’s own (autologous) HSCs are used for transplant, but in some patients, their HSCs cannot be mobilized in sufficient numbers using the growth factor G-CSF (granulocyte colony-stimulating factor) to enable a successful transplant. In a new study, Ferraro and colleagues set out to discover the causes of this poor HSC mobilization.

The investigators discovered by analyzing data from a number of bone marrow transplant patients that patients with diabetes showed poorer mobilization of HSCs in response to G-CSF than did those patients who did not have diabetes. The authors then confirmed in mouse models of type 1 and type 2 diabetes that HSCs were poorly mobilized from the bone marrow in response to G-CSF in these mice but not healthy control animals. The authors discovered that there was a defect in the bone marrow microenvironment of the diabetic mice rather than a problem with the HSCs themselves. Specifically, in diabetic (but not control) mice, the researchers observed mislocalization of HSCs in the bone marrow and an increase in the number of perivascular sympathetic nerve fibers in the niche with a concomitant inability of bone marrow mesenchymal stem cells to down-modulate production of the chemokine CXCL12 (a molecule known to mediate HSC localization). Finally, the authors were able to overcome the defect in HSC mobilization using a clinically approved drug called AMD3100 that interrupts the interaction of CXCL12 with its receptor CXCR4. The authors suggest that AMD3100 could be used to boost HSC mobilization in diabetic patients who require a bone marrow transplant.

Footnotes

  • * These authors contributed equally to this work.