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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2003-01-0318.
Submitted January 31, 2003
Accepted March 11, 2003
The mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure
Janis L Abkowitz*, Abigail E Robinson, Sujata Kale, Michael W Long, and Jing Chen
Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA
Department of Pediatrics, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA
* Corresponding author; email: janabk{at}u.washington.edu.
We created parabiotic mice, joining ROSA26 and PeP3b animals, to study the trafficking of hematopoietic stem cells (HSC) from marrow to blood and their return to marrow. The transfer of HSC was assayed by secondary marrow transplantation and was 1.0-2.5% after 3, 6, 8 and 12 weeks. Thus, HSC homeostasis is primarily maintained by the retention of stem cells derived from replication events within the marrow, and not the homing and engraftment of HSC from the circulation. Of interest, the phenotype of marrow progenitors and granulocytes were similar to HSC, implying that the marrow functions as an intact compartment where differentiating cells derive from endogenous HSC. In contrast, 50% of splenic granulocytes and progenitor cells derived from the parabiotic partner, suggesting splenic progenitor cells were in constant equilibrium with progenitors in blood. In additional studies, animals were exposed to G-CSF and stem cell factor at days 17-20 of parabiosis, then studied 3 weeks later. 10.1% of marrow HSC derived from the parabiotic partner. These data imply that HSC, mobilized to the blood in response to cytokine exposure, are destined to later return to marrow, an observation which supports the concept that the mobilized peripheral blood stem cells used in clinical transplantation function physiologically.
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