Flt3-ligand-mobilized peripheral blood, but not Flt3-ligand-expanded bone marrow, facilitating cells promote establishment of chimerism and tolerance

Stem Cells
Yiming HuangSuzanne T Ildstad

Abstract

Facilitating cells (CD8+/TCR-) (FCs) enhance engraftment of limiting numbers of hematopoietic stem cells (HSCs). The primary component of FCs is precursor-plasmacytoid dendritic cells (p-preDCs), a tolerogenic cell expanded by Flt3-ligand (FL). In this study, we evaluated the function and composition of FL-expanded FCs. FL treatment resulted in a significant increase of FCs in bone marrow (BM) and peripheral blood (PB). When FL-expanded FCs were transplanted with c-Kit+/Sca-1+/Lin- (KSL) cells into allogeneic recipients, BM-FCs exhibited significantly impaired function whereas PB-FCs were potently functional. A significant upregulation of P-selectin expression and downregulation of VCAM-1 (vascular cell adhesion molecule 1) were present on FL-expanded PB-FCs compared with FL BM-FCs. Stromal cell-derived factor-1 (SDF-1), and CXCR4 transcripts were significantly increased in FL PB-FCs and decreased in FL BM-FCs. Supernatant from FL PB-FCs primed HSC migration to SDF-1, confirming production of the protein product. The FL PB-FCs contained a predominance of p-preDCs and natural killer (NK)-FCs, and NK-FCs were lacking in FL BM-FCs. The impaired function for BM-FCs was restored within 5 days after cessation of treatment. Taken toge...Continue Reading

Citations

Jan 20, 2010·Immunology and Cell Biology·Noorjahan Banu AlitheenPeter McCullagh
Jul 25, 2006·Nature Methods·Tenneille E LudwigJames A Thomson
May 26, 2006·Nature Reviews. Molecular Cell Biology·Eran Meshorer, Tom Misteli
Aug 24, 2007·Reproduction, Fertility, and Development·R Tayfur Tecirlioglu, Alan O Trounson
Mar 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Sybill Thomas-EckerThomas Dittmar
Apr 9, 2008·Stem Cells and Development·Ugur SalliKent E Vrana

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