THE BROAD-SPECTRUM OF CYTOKINE GENE-EXPRESSION BY MYOID CELLS FROM THE HUMAN MARROW MICROENVIRONMENT

Nontransformed stromal colony-derived cell lines (CDCLs) consist of a pure stromal cell population that differentiates following a vascular smooth muscle cell repertoire, and whose in vivo counterpart is that o f myoid cells found in adult and fetal human bone marrow cords, We stu died the cytokine expression by reverse-transcriptase polymerase chain reaction (RT-PCR) from pooled fast-growing clones from 10 different b one marrow samples, RT-PCR indicated that 30 cytokines (out of 42 stud ied) mere expressed by CDCLs (20 after medium renewal and hydrocortiso ne renewal, three after addition of interleukin 1 beta (IL-1 beta) and seven in only part of the CDCL layers examined), The cytokines expres sed comprised mediators known to be involved in the maintenance of ear ly and late hematopoiesis (IL-1 alpha and IL-beta, IL-6, IL-7, IL-8, I L-11 and IL-13; colony-stimulating factors, thrombopoietin, erythropoi etin, stem cell factor, fit 3-ligand, hepatocyte cell growth factor, t umor necrosis factor alpha, leukemia inhibitory factor, transforming g rowth factors beta 1 and beta 3; and macrophage inflammatory protein 1 alpha), angiogenic factors (fibroblast growth factors 1 and 2, vascul ar endothelial growth factor) and mediators whose usual target (and so urce) is the connective tissue-forming cells (platelet-derived growth factor ii, epidermal growth factor, transforming growth factors alpha and beta 2, oncostatin M and insulin-like growth factor 1), or neurona l cells (nerve growth factor), The cytokines not expressed mere lympho kines (IL-2, IL-3, IL-4, IL-5, IL-9, IL-10, and IL-12 and interferon g amma) or mediators synthesized by macrophages (inhibin, activin, plate let-derived growth factor B, and IL-I receptor antagonist), This study complements the description of the phenotype of the myoid cells, conf irming that these cells are the marrow connective tissue-forming cells ; moreover, this work suggests that stromal control of hematopoiesis i s multifactorial and that myoid cells are involved in the control of m arrow angiogenesis and innervation.