Umbilical cord blood from preterm human fetuses is rich in committed and primitive hematopoietic progenitors with high proliferative and self-renewalcapacity

Human umbilical cord blood (CB) has been recognized as a source of hematopo ietic stem cells for transplantation. While hematopoietic properties of neo natal CB from full-term pregnancies have been well characterized, little is known about CB from early gestational ages. We analyzed the content and th e growth properties of primitive and committed hematopoietic progenitors in preterm CB from second trimester (week 16-28; n = 17) and early third trim ester (week 29-34; n = 17) in comparison with term CB (n = 18). The frequen cy of CD34(+) and CD34(+)CD38(-) cells was significantly higher in preterm than in term CB (mean, 2.51% and 0.56% vs 0.88% and 0.13%; p < 0.002), The number of colony forming units (CFU) in preterm CB was about twofold higher (230 +/- 6 vs 133 +/- 14/10(5) mononuclear cells; p < 0.05) and correlated with the content of CD34(+) progenitors (r = 0.73), Long-term culture init iating cells (LTC-IC) were enriched about 2.5-fold (6.7 +/- 2.9 vs 2.6 +/- 1.2/10(5) cells; p < 0.05), Progenitors from preterm CB could be expanded i n stroma-free liquid cultures supplemented with hematopoietic growth factor s as efficiently as progenitors from term neonates, Tn short-term cultures containing erythropoietin (Epo), interleukin (IL)-1, IL-3, and IL-6, or gra nulocyte- (G-) and granulocyte-macrophage colony-stimulating factor (GM-CSF ) together with stem cell factor (SCF) or Flt3 ligand (FL), expansion of CF Us was six- to eightfold at week 1, In long-term cultures containing thromb opoietin (TPO) and FL, an approximately 1000-fold expansion of multilineage progenitors was observed at week 10, In summary, we show that preterm CB c ompared with term CB is richer in hematopoietic progenitors, and that precu rsors from preterm CB can be extensively expanded ex vivo. This may have im plications for the development of transplantation and gene transfer strateg ies targeting circulating fetal stem cells. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.