Nontransformed colony-derived stromal cell lines from normal human marrows. III. The maintenance of hematopoiesis from CD34+ cell populations.

Nontransformed stromal colony-derived cell lines (CDCLs) consist of a pure stromal cell population that differentiates following a vascular smooth-muscle cell repertoire. Here we study the maintenance of hematopoiesis by this cell population. We show that CDCLs allow the generation for several weeks of stroma-adherent colonies (comprising a cobblestone area) from CD34+, CD34+/CD38+, and CD34+/CD38- cells. Stroma-adherent colony-forming cells (CFCs) from CD34+/CD38- cells reach a maximum at week 4 and limiting dilution analysis gives a frequency of 1 per 10 cells seeded; in contrast to this, CFCs from CD34+/CD38+ cells are optimal by week 2 and the frequency is then only 1 per 120 cells seeded. Stroma-adherent colonies comprise hematopoietic cells from all lineages except the T lymphocytic, with a majority of granulomonocytes. CDCLs also allow the amplification of granulomonocytic colony-forming units (CFU-GMs), since cumulative outputs of CFU-GMs by week 6 are 190 and 8 times that observed at culture inception for the CD34+/CD38- and CD34+/CD38+ cell populations, respectively. Our results suggest that stromal cells from CDCLs allow the maintenance of primitive hematopoietic precursors and induce their proliferation and differentiation. This study underscores the potential role of one of the microenvironmental cell populations, that of myoid cells, in the regulation of hematopoietic precursor behavior.