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Regulation of Stroma Function: Role of CD44
The clonal stromal cell line, S17, derived from bone marrow,
maintains high levels of repopulating
stem cells. We found that the support
capacity of this line can be regulated via the cell surface molecule CD44.
Using CD44-specific mAb, we found that stem cell support can be either suppressed
or enhanced depending on the epitope of CD44 detected by the mAb. Using
genetic tools we showed that the enhancing effect is specific for the stroma
while the suppressive effect act on the hematopoietic compartment. Both
effects involve signal transduction in the target cell compartment. Thus,
CD44, believed to be an adhesion molecule, has unexpected regulator roles
in stem cell maintenance. To identify the physiological ligands for the
CD44 epitopes we are screening a panel of extracellular matrix molecules
and peptide libraries. We anticipate that potential ligands will have therapeutic
applications in improving recovery of stem cells after marrow ablation. Stromal Cell Regulation of Stem Cell Maintenance Establishment of Stroma: Role of M-SCF Regulation of Stroma Function: Role of CD44
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