In Vitro Behavior of Hematopoietic Progenitor Cells Under the Influence of Chemoattractants: Stromal Cell–Derived Factor-1, Steel Factor, and the Bone Marrow Environment

Abstract

How multiple chemoattractants cooperate in directing the migration of hematopoietic progenitor cells (HPC) for homing and peripheral blood mobilization has not yet been established. We report here the behavior of HPC under the influence of two different chemoattractants, stromal cell-derived factor (SDF)-1 and steel factor (SLF), and the chemotactic nature of the bone marrow (BM) environment using a two-chamber in vitro migration system. Various formulae were adopted to quantitate these effects. Based on these quantitations, SDF-1 showed only chemotactic activity, while SLF showed both chemotactic and chemokinetic activities on factor-dependent MO7e cells. SLF, like SDF-1, attracted human HPC from a population of CD34+ cells and induced actin polymerization in MO7e cells. SLF and SDF-1 cooperated in attracting MO7e cells, as well as cord blood (CB) and BM CD34+cells. A negative concentration gradient of SLF and SDF-1, formed by the presence of chemoattractants in the upper chamber, showed potent inhibitory effects on MO7e cell migration induced by either of these chemoattractants in the lower chamber, and SDF-1 and SLF were synergistic in mobilizing cells to the lower chamber from this negative chemoattractant gradient. Plasma obtained from BM aspirates, but not CB or peripheral blood, showed strong chemotactic effects on BM and CB CD34+ cells, and an inhibitory effect in a negative gradient on SDF-1–dependent CD34+ cell migration. These in vitro migration experiments suggest that chemoattractants such as SDF-1 and SLF with other unidentified BM chemoattractants may be involved cooperatively in the migration of HPC to the BM and in preventing spontaneous mobilization of HPC out of the BM.