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 Blood, 29 October 2009, Vol. 114, No. 18, pp. 3773-3782.
Prepublished online as a Blood First Edition Paper on September 1, 2009; DOI 10.1182/blood-2009-05-219840.

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HEMATOPOIESIS AND STEM CELLS

On the adaptation of endosteal stem cell niche function in response to stress

Yi Jiang1, Halvard Bonig1,2, Tatiana Ulyanova1, KaiHsin Chang1, and Thalia Papayannopoulou1

1 University of Washington, Department of Medicine/Hematology, Seattle; and 2 German Red Cross Blood Center and Institute for Transfusion Medicine and Immunohematology, Johann-Wolfgang-Goethe University, Frankfurt, Germany

Although the influence of microenvironmental "niche" on the function of a variety of stem cells is undisputed, the details of hematopoietic stem cell/niche interactions at the cellular and molecular level have sparked a continuous debate. We studied the microanatomic partitioning of transplanted normal and {alpha}4 integrin-deficient Lin–kit+ cells in trabecular and compact bone before and after irradiation and present robust quantitative data on both. We found that (1) the microanatomic distribution of normal highly enriched progenitor cells is random in nonirradiated recipients based on area distribution analyses, (2) in contrast, in irradiated hosts normal cells distribute preferentially near the endosteum, (3) the overall cell seeding efficiency was higher in trabecular versus compact bone both before and after irradiation, and (4) {alpha}4 integrin-deficient cells not only lodge with reduced overall efficiency confirming previous data, but fail to preferentially partition themselves into endosteal regions in irradiated hosts, as normal cells do. A similar phenotype was observed with cells rendered Gi-protein signaling incompetent by pertussis toxin treatment, supporting an active stromal-derived factor 1 (SDF-1) gradient near endosteum after irradiation.


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