IN-VITRO EXPANSION OF HEMATOPOIETIC STEM-CELLS

We have investigated the effects of interleukin 3 (IL-3) and IL-1 on i n vitro expansion of murine hematopoietic progenitors and stem cells u sing a highly purified progenitor population. Lineage negative, Ly-6A/ E+, c-kit(+) bone marrow cells from male mice were cultured in suspens ion in the presence of stem cell factor, IL-6, IL-11 and erythropoieti n with or without IL-3 or IL-1. An exponential increase in total nucle ated cell counts and about a 10-fold enhancement of nucleated cells by IL-3 were observed during the initial 10 days. Addition of IL-3 haste ned the development but significantly suppressed the peak production o f colony-forming cells. Addition of IL-1 also significantly suppressed the numbers of progenitors. We then tested the reconstituting ability of the cultured cells by transplanting cells together with ''compromi sed'' marrow cells into lethally irradiated mice. The cells expanded f rom enriched cells in the absence of IL-3 or IL-1 revealed engraftment at two, six and 10 months, while addition of IL-3 or IL-1 to the cult ures significantly reduced the reconstituting ability. IL-3 and IL-1 m ay have negative modulatory effects on the self-renewal of stem cells.