Stromal cell-derived factor-1/CXCL12 directly enhances survival/antiapoptosis of myeloid progenitor cells through CXCR4 and Gαi proteins and enhances engraftment of competitive, repopulating stem cells

Abstract

Stromal cell‐derived factor‐1 (SDF‐1/CXCL12) enhances survival of myeloid progenitor cells. The two main questions addressed by us were whether these effects on the progenitors were direct‐acting and if SDF‐1/CXCL12 enhanced engrafting capability of competitive, repopulating mouse stem cells subjected to short‐term ex vivo culture with other growth factors. SDF‐1/CXCL12 had survival‐enhancing/antiapoptosis effects on human bone marrow (BM) and cord blood (CB) and mouse BM colony‐forming units (CFU)‐granulocyte macrophage, burst‐forming units‐erythroid, and CFU‐granulocyte‐erythroid‐macrophage‐megakaryocyte with similar dose responses. The survival effects were direct‐acting, as assessed on colony formation by single isolated human BM and CB CD34⁺⁺⁺ cells. Effects were mediated through CXCR4 and Gαi proteins. Moreover, SDF‐1/CXCL12 greatly enhanced the engrafting capability of mouse long‐term, marrow‐competitive, repopulating stem cells cultured ex vivo with interleukin‐6 and steel factor for 48 h. These results extend information on the survival effects mediated through the SDF‐1/CXCL12–CXCR4 axis and may be of relevance for ex vivo expansion and gene‐transduction procedures.