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The Spleen Contributes Stem Cells to Peripheral Blood Stem Cell Transplants

Toshiyuki Mera, Shelly Heimfeld and Denise L Faustman

Treatment of malignancies with Peripheral Blood Stem Cell Transplants (PBSCTs) from donors given Granulocyte- Colony-Stimulating-Factor (G-CSF) has improved survival relative to bone marrow transplants. G-CSF mobilizes CD34+ hematopoietic stem cells from bone marrow into the blood. Enrichment of PBSCT by purification of CD34+ stem cells fails to produce superior clinical benefits. We hypothesize that the reason why CD34+-enriched PBSCTs are not more effective is because the enrichment and purification process leaves out G-CSF-mobilized stem cells from another source, the spleen, which holds a unique reservoir of Hox11+ stem cells. Quantitative mRNA analysis was used to determine whether G-CSF mobilizes Hox11+ stem cells and whether expression occurs in a cell population distinct from CD34+ cells. Samples of peripheral blood lymphocytes (PBLs) were obtained from ten normal untreated donors and 18 normal donors treated with G-CSF. G-CSF was found to mobilize both CD34+ stem cells (p=0.02) and even more dramatically mobilize Hox11+ splenic stem cells (p=0.000013) into the peripheral blood. The findings support the hypothesis that G-CSF mobilizes two distinct stem cell populations, one from the bone marrow and the other from the spleen. The inferior clinical performance of CD34+-enriched and purified PBSCTs compared to unenriched PBSCTs may be explained by the omission of Hox11+ stem cells. These findings suggest that PBSCTs without enrichment and purification of CD34+ may improve treatment of cancer and potentially other diseases in tissues derived from Hox11+ stem cells.