Thrombopoietin stimulates murine lineage negative, Sca-1(+), C-Kit(+), CD34(-) cells: comparative study with stem cell factor or interleukin-3

It has recently been reported that human thrombopoietin (TPO) acts on early hematopoietic progenitor cells. Consequently, we investigated the effects of TPO on murine hematopoietic progenitor cells using lineage negative (Lin (-)), Sca-1(+), c-Kit(+) marrow cells from 5-fluorouracil-treated mice. One hundred enriched cells were cultured in suspension with various single cyt okines for 5 days. When cultured with the single cytokines as stem cell fac tor (SCF),TPO, or interleukin (IL)-3, these cells were maintained or had in creased by day 5, whereas only a few cells survived in cultures with granul ocyte colony stimulating factor, IL-11, or IL-6. We extended the study in s erum-free or serum-containing suspension cultures with SCF or TPO. Anti-TPO antibodies did not inhibit the effects of SCF on enriched cells but did in hibit the effects of TPO on those cells. We further examined the effects of TPO, SCE and IL-3 on other populations of murine hematopoietic progenitor cells. Either TPO or SCF as a single cytokine could maintain murine Lin(-), Sea-1(+), c-Kit(+), CD34(-) marrow cells, which are the most dormant cells . In addition, IL-3 increased Lin(-), Sca-1(-), c-Kit(+) cells more than di d SCF and TPO but did not stimulate Lin(-), Sea-1(+), c-Kit(+), CD34- cells more. These results indicate that TPO as well as SCF may be key regulators in the proliferation of murine hematopoietic early progenitor cells. (C) 2 000 The Japanese Society of Hematology.