Platelet‐derived growth factor stimulates growth of highly enriched multipotent haemopoietic progenitors

Abstract

Platelet-derived growth factor (PDGF) has been shown to stimulate growth of normal and malignant fibroblasts, glial cells and smooth muscle cells. A growth promoting effect on human haemopoietic precursors has also been described, but the interpretation of this haemopoietic proliferative response to PDGF has been hampered by the lack of purity of the target population. In this study we show that PDGF promotes growth of early bone marrow haemopoietic progenitors depleted of either monocytes or T lymphocytes which are known to influence haemopoiesis. Moreover, the action of PDGF is even increased on a highly enriched BI-3C5 early bone marrow population. BI-3C5 is a novel monoclonal antibody which recognizes an antigen present on all multilineage colony-forming cells (CFU-mix) (Tindle et al. 1985). BI-3C5 positively and negatively sorted fractions were obtained by fluorescence activated cell sorting (FACS) and PDGF was found to stimulate growth of CFU-mix in the BI-3C5-positive fraction (consisting of only 4-6% of the marrow population), the effect being more marked than that on unsorted bone marrow. The results suggest that the product of the cellular proto-oncogene c-sis (the putative structural gene for the beta chain of PDGF) may play a regulatory role in the in vivo proliferation of multipotent haemopoietic progenitors.

Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF β-receptor null mice

“…19,21,[32][33][34] PDGF promotes in vitro proliferation of erythropoietic progenitors, 20 but stimulation requires the presence of adherent stromal cells, 21 presumably because of PDGF induction of colony-stimulating factor (CSF) release from the stromal cells. Mouse splenic erythroid cells express PDGF in vivo after stimulation with erythropoietin, 17,18 demonstrating that precursors of the erythroid lineages are a source of PDGF.…”

“…Mouse splenic erythroid cells express PDGF in vivo after stimulation with erythropoietin, 17,18 demonstrating that precursors of the erythroid lineages are a source of PDGF. In mixed marrow cultures, PDGF stimulates the growth of primitive hematopoietic progenitor cells, such as colony-forming units containing granulocytes, erythroid cells, macrophages, megakaryocytes (CFU-mix, CFU-GEMM), 19,32,33 and lineage-restricted hematopoietic progenitors. 34 Adherent accessory cells are also required for the stimulation of primitive and lineage-restricted hematopoietic progenitors by PDGF, and growth enhancement appears to occur as an indirect effect through the stimulation of interleukin-1 (IL-1) production by PDGFR-positive stromal cells, including macrophages.…”

Autocrine Expression of Platelet-Derived Growth Factor B in B Cell Chronic Lymphocytic Leukemia

“…Coexpression of PDGF and PDGF receptors has been observed in various human tumors, including meningiomas, melanomas, neuroendocrine tumors, ovarian cancer, pancreatic cancer, gastric cancer, lung cancer and prostate cancer [7]. PDGF can enhance proliferation of normal hematopoietic cells [8, 9] and of hematologic malignancies, such as acute myeloid leukemia [10], chronic myeloid leukemia [11] and myeloproliferative disorders [12]. Tsai et al [13] reported that the pre-B cell line of acute lymphocytic leukemia produces PDGF-A and its receptor in lymphoid malignancies, and they implied that PDGF may function as a lymphokine.…”

Platelet-derived growth factor enhances ex vivo expansion of megakaryocytic progenitors from human cord blood

“…PDGF also promotes in vitro multipotent haematopoietic progenitors and erythropoiesis. 23,24 In previous studies, we demonstrated the presence of functional PDGF receptors on human MK and MK cell lines 25 and showed that PDGF promoted MK colony formation. 26 In this study, we aimed to establish a cytokine combination for the efficient ex vivo expansion of the MK lineage from umbilical cord blood CD34 + cells, and to investigate the effect of PDGF in this system.…”