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Stem cell factor (SCF) synergizes with megakaryocyte colony stimulating activity in post-irradiated aplastic plasma in stimulating human megakaryocytopoiesis

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Abstract

Plasma obtained from lethally irradiated animals contains a megakaryocyte (MK) growth factor which has recently been identified as the ligand for the c-mpl receptor and has been named thrombopoietin (TPO). We demonstrate that post-irradiation aplastic canine plasma (PICS-J) and plasma from a human subject (ML) who was accidentally exposed to lethal irradiation, contain high levels of this activity, which support both MK proliferation and maturation in a dose-dependent manner. These plasma were far more active in stimulating human MK colony formation than other types of thrombocytopenic plasma or a number of exogenously added human recombinant cytokines and their combinations. The addition of stem cell factor (SCF), which alone has a minimal stimulatory affect, to post lethal-irradiation plasma provided a synergistic stimulation of megakaryocytopoiesis both in colony assays and liquid cultures. In colony assays, the combination of SCF with PICS-J or ML almost doubled the number of burst forming units (BFU-MK) and provided a 1.5-fold increase in colony forming units (CFU-MK). A 1.6-fold increase in the number of CD34+ BM cell-derived MK colonies was also elicited. In liquid cultures, the presence of both SCF and PICS-J or ML induced the appearance of a high proportion of CD34+ (6.56% vs 0.6% control) and CD41+ (3.5% vs 1.2% control) cells after 3 days in culture. By day 10, 66.8 xl04 CD41+ cells and 29.8xl04 CD34+ cells were derived from 2x106 BMMC originally seeded. We propose that these unique plasma, which do not contain elevated levels of IL-6, IL-3, GM-CSF, IL-1β, erythropoietin or SCF, probably contain high levels of TPO. The addition of SCF to the post-irradiation plasma provides a synergistic stimulation of megakaryocytopoiesis which may become relevant for future clinical application.

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Authors and Affiliations

  1. Department of Hematology, Department of Bone Marrow Transplantation and the Oncology Department, Hadassah University Hospital, 91120, Jerusalem, Israel

    Varda R. Deutsch, Vivian Barak & Arnon Nagler

  2. Hematology Institute, Tel Aviv Medical Center, Tel Aviv, Israel

    Varda R. Deutsch, Amiram Eldor & Marjorie Pick

  3. Department of Hematology, Children’s Hospital, Columbus, Ohio, USA

    Tom Olson

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  1. Varda R. Deutsch
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  2. Amiram Eldor
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Deutsch, V.R., Eldor, A., Olson, T. et al. Stem cell factor (SCF) synergizes with megakaryocyte colony stimulating activity in post-irradiated aplastic plasma in stimulating human megakaryocytopoiesis. Med Oncol 13, 31–42 (1996). https://doi.org/10.1007/BF02988839

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