CD34(+) cord blood cells expressing cutaneous lymphocyte-associated antigen are enriched in granulocyte-macrophage progenitors and support extensive amplification of dendritic cell progenitors

Objective. We evaluated the frequency of hematopoietic progenitor cells (HP C) in CD34(+)CLA(+) (cutaneous lymphocyte-associated antigen) and CD34(+)CL A(-) cord blood cells, and followed cellular growth and HPC production duri ng cultures in Flt3 ligand, thrombopoietin, and stem cell factor (FTS). Materials and Methods. Immunomagnetic bead-purified CD34(+) cells were sort ed into CD34(+)CLA(+) or CD34(+)CLA(-) cells. HPC frequency was assessed by clonal assays in methylcellulose either ex vivo or after, 7, 14, or 21 day s of culture with FTS. Dendritic cell (DC) progenitors were evaluated after induction of FTS-amplified cells into DC using secondary cultures containi ng granulocyte-macrophage colony-stimulating factor and interleukin-4. Results. Ex vivo, granulocyte-macrophage progenitors were more frequent and erythroid progenitors were less frequent in the CLA(+) fraction. In FTS cu lture, CD34(+)CLA(+) cells produced greater absolute numbers of CD34(+) cel ls, granulocyte-macrophage-, erythroid-, and DC (including Langerhans cell- related) progenitors compared to CD34(+)CLA(-) cells. In CD34(+)CLA(+) cult ures, CLA(+) cells steadily decreased with time, and CD34(+)CLA(-) cells ap peared. In CD34(+)CLA(-) cultures, CLA(+) cells were generated, increased u p to day 7, and decreased thereafter. CLA was expressed only on CD34(-) cel ls in these cultures. Ex vivo, CD34(+)CLA(+) cells could be subdivided furt her into CD38(low) and CD38(high) cells. Cord blood and growth factor-mobil ized CD34(+) cells contained more CLA(+)CD38(low) cells than nonmobilized p eripheral blood CD34(+) cells and proliferated more extensively with FTS th an the latter cells. Conclusions. CD34(+)CLA(+) cells contain a rather immature progenitor capab le of high proliferation and extensive amplification of HPC in vitro. This progenitor may be localized in the CD34(+)CLA(+)CD38(low) fraction. In addi tion, cultures of CD34(+)CLA(+) cells from cord blood produced CD34(-)CLA(- ) cells, suggesting that these cells may derive directly from CD34(+)CLA(+) cells in vivo. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.