Murine M2-10B4 and SL/SL cell lines differentially affect the balance between CD34(+) cell expansion and maturation

The ability of bone marrow stroma to modulate hematopoietic progenitor cell expansion is of considerable interest for gene transfer strategies and tra nsplantation of limited stem cell numbers. We compared the capacity of 2 mu rine stromal cell lines to affect the balance between maturation and prolif eration of human CD34(+) cells in short-term expansion cultures. In 7-day s erum-free cultures, cytokine-induced amplification of granulocyte-macrophag e colony-forming cells (CFC-GM), erythroid burst-forming units (BFU-E), and total cells was significantly increased by the presence of genetically eng ineered S1/S1 and M2-10B4 stromal cells in a 1:1 ratio (S1/M2 cells) compar ed with stroma-free cultures (P < .05). S1/M2 cultures generated 21-fold mo re mature CD15(+) cells than stroma-free cultures, without further amplifyi ng the number of CD34(+) cells. The addition of serum led to a further incr ease of CFC-GM total cells, and CD15(+) cells, whereas BFU-E were no longer maintained. Pure S1/S1 stromal layers were likewise superior to stroma-fre e cultures in expansion of CD34(+) cells and total cells when serum was pre sent. However, the differentiation of CD34(+) cells was less pronounced in S1/S1 cultures compared with S1/M2 layers, as demonstrated by a lower conte nt of CD15(+) cells. Neutralization experiments revealed differential contr ibutions of Flt3 ligand and thrombopoietin to the support of total cell and CFC expansion by S1/M2 and S1/S1 stromal feeders. (C) 2001 The Japanese So ciety of Hematology.