Thrombopoietin, but not erythropoietin promotes viability and inhibits apoptosis of multipotent murine hematopoietic progenitor cells in vitro

The recently cloned c-mpl ligand, thrombopoietin (Tpo), has been extensively characterized with regard to its ability to stimulate the growth, development, and ploidy of megakaryocyte progenitor cells and platelet production in vitro and in vivo. Primitive hematopoietic progenitors have been shown to express c-mpl, the receptor for Tpo. In the present study, we show that Tpo efficiently promotes the viability of a subpopulation of Lin(-)Sca-1(+) bone marrow progenitor cells, The ability of Tpo to maintain viable Lin(-)Sca-1(+) progenitors was comparable to that of granulocyte colony-stimulating factor and interleukin-l, whereas stem cell factor (SCF) promoted the viability of a higher number of Lin(-)Sca-1(+) progenitor cells when incubated for 40 hours. However, after prolonged (>40 hours) preincubation, the viability-promoting effect of Tpo was similar to that of SCF, An increased number of progenitors surviving in response to Tpo had megakaryocyte potential (37%), although almost all of the progenitors produced other myeloid cell lineages as well, suggesting that Tpo acts to promote the viability of multipotent progenitors. The ability of Tpo to promote viability of Lin(-)Sca-1(+) progenitor cells was observed when cells were plated at a concentration of 1 cell per well in fetal calf serum-supplemented and serum-depleted medium. Finally, the DNA strand breakage elongation assay showed that Tpo inhibits apoptosis of Lin(-)Sca-1(+) bone marrow cells. Thus, Tpo has a potent ability to promote the viability and suppress apoptosis of primitive multipotent progenitor cells. (C) 1996 by The American Society of Hematology.