Prostaglandin-mediated enhancement of erythroid colonies by marrow stromal cells (MSC)

Abstract

Marrow stromal cells (MSC) released a diffusible substance in split-phase culture that enhanced the response of erythroid colonies to erythropoietin when MSC were present in small numbers and suppressed when they were present in large numbers. Incremental concentrations of indomethacin inhibited the enhancement, but it did not suppress growth of MSC colonies. Radioimmunoassay of conditioned media demonstrated that MSC produced E-type prostaglandin (PGE) that was inhibited by non-lethal concentrations of indomethacin sufficient to suppress MSC enhancement of erythroid colonies. Finally, when increasing concentrations of PGE2 were added to cultures, erythroid colonies were enhanced at levels similar to those produced by small numbers of MSC which enhanced and suppressed at higher levels, producing a biphasic curve similar to that noted with increasing numbers of MSC in the underlayer. These data support our hypothesis that E-type prostaglandins are released by marrow stromal cells (MSC) to mediate the enhancement and suppression of erythroid colonies, in vitro.