INTERLEUKIN-3 OR INTERLEUKIN-1 ABROGATES THE RECONSTITUTING ABILITY OF HEMATOPOIETIC STEM-CELLS

Because of their known myelopoietic activities, both interleukin (IL)- 3 and IL-1 are often used in combination with other cytokines for in v itro (ex vivo) expansion of stem cells. We have investigated the effec ts of IL-3 and IL-1 on in vitro expansion of murine hematopoietic stem cells with long-term engraftment capabilities, using a highly purifie d progenitor population. Lineage-negative, Ly-6A/E(+), c-kit(+) bone m arrow cells from male mice were cultured in suspension in the presence of stem cell factor, IL-6, IL-11, and erythropoietin with or without IL-3 or IL-1. Kinetic studies revealed an exponential increase in tota l nucleated cells and about 10-fold enhancement of nucleated cells by IL-3 during the initial 10 days. Addition of IL-3 hastened the develop ment but significantly suppressed the peak production of colony-formin g cells. Addition of IL-1 also significantly suppressed the numbers of colony-forming cells. The reconstituting ability of the cultured cell s was tested by transplanting the expanded male cells into lethally ir radiated female mice, The cells expanded from enriched cells in the ab sence of IL-3 and IL-1 revealed engraftment at 2, 4, 5, and 6 months, whereas addition of IL-3 or IL-1 to the cultures significantly reduced the reconstituting ability. The results suggest that these cytokines mag. have a modulatory role on the self-renewal of stem cells and furt her indicate that the use of IL-3 and IL-1 for in vitro expansion of h uman stem cells needs to be cautiously evaluated.