Quantitative and qualitative differences in thrombopoietin-dependent hematopoietic progenitor development between cord blood and bone marrow

BACKGROUND: To assess the clinical application of thrombopoietin (TPO) for thrombocytopenia of patients receiving cord blood (CB) or bone marrow (BM) transplants, we examined whether various types of hematopoietic progenitors including megakaryocyte (MK) progenitors from CB and BM exerted different proliferative and differentiative potential in the presence of TPO. METHODS: The development of MK, granulocyte-macrophage, and erythroid/mixed erythroid (E/Mix) progenitors in a serum-deprived liquid culture medium supplemented with TPO was compared between CD34+ CB and BM cells. RESULTS: The CD34+ CB cells generated 30-fold more MKs than the CD34+ BM cells, but the CB-derived MKs were more immature. A single-cell culture study showed that CB CD34+CD38- cells as well as CD34+CD38+ cells proliferated in response to TPO, whereas the two subpopulations of CD34+ BM cells showed little multiplication. In short-term liquid cultures containing CD34+ CB or BM cells, TPO significantly increased the absolute numbers of various types of colony-forming cells, compared with the input values. In particular, MK progenitors and E/Mix progenitors in CB were amplified to a substantially greater extent than in BM. The superior response of CD34+ CB cells to TPO observed in this study may be due in part to the use of cryopreserved cells. CONCLUSIONS: Our results suggest that TPO alone cannot only stimulate megakaryocytopoiesis but also increase the numbers of various types of hematopoietic progenitors, and that quantitative and qualitative differences in TPO-dependent hematopoietic progenitor development exist between CB and BM.