EX-VIVO EXPANSION WITH STEM-CELL FACTOR AND INTERLEUKIN-11 AUGMENTS BOTH SHORT-TERM RECOVERY POSTTRANSPLANT AND THE ABILITY TO SERIALLY TRANSPLANT MARROW

The characterization of many cytokines involved in the control of hema topoiesis has led to intense investigation into their potential use in ex vivo culture to expand progenitor numbers. We have established the optimum ex vivo culture conditions that allow substantial amplificati on of transient engrafting murine stem cells and which, simultaneously , augment the ability to sustain serial bone marrow transplantation (B MT). Short-term incubation of unfractionated BM cells in liquid cultur e with stem cell factor (SCF) and interleukin-ll (IL-ll) produced a 50 -fold amplification of clonogenic multipotential progenitors (CFU-A). Following such ex vivo expansion, substantially fewer cells were requi red doses above threshold for engraftment, BM cells expanded ex vivo r esulted in significantly more rapid hematopoietic recovery. In a seria l transplantation model, unmanipulated BM was only able to consistentl y sustain secondary BMT recipients, but BM expanded ex vivo has sustai ned quaternary BMT recipients that remain alive and well more than 140 days after 4 degrees BMT. These results show augmentation of both sho rt-term recovery posttransplant and the ability to serially transplant marrow by preincubation in culture with SCF and IL-ll. (C) 1996 by Th e American Society of Hematology.