Induction of apoptotic change of hematopoietic cells by cloned stromal cells from mds patient via direct cellular interactions

Abstract We previously reported on the heterogeneity of bone marrow stromal cell function in supporting hematopoietic cell proliferation and differentiation in vitro among refractory anemia (RA) of myelodysplastic syndrome (MDS) patients. Interestingly, stromal cells from same MDS RA patients induced an apoptotic change in CD34-positive hematopoietic cells (CD34+). To clarify the mechanism of this action of stromal cells, a cloned stromal cell line (LS801) from MDS patient was established. In a coculture system with LS801, proliferation and differentiation of CD34+ cells was inhibited. Assay for the expression of 7A6 antigen on CD34+ cells, for monitoring the cells undergoing apoptosis, showed that LS801 induced an apoptotic change in CD34+ cells. When CD34+ cells were cocultured but kept separate fom LS801 by a 0.45-mm millipore membrane to prevent their attachment, the action of LS801 for inducing apoptosis of CD34+ cells was inhibited. The expression of CD95 on CD34+ cells was induce by LS801, however, no production of fas ligand, TNF-α or IFN-γ in LS801 was observed. In light of these observations, direct contact between LS801 and CD34+ cells might be essential for maximum induction of CD34+ cells undergoing apoptosis.