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

Human umbilical cord blood (CB) has been recognized as a source of hematopoietic stem cells for transplantation. While hematopoietic properties of neonatal CB from full-term pregnancies have been well characterized, little is known about CB from early gestational ages. We analyzed the content and the growth properties of primitive and committed hematopoietic progenitors in preterm CB from second trimester (week 16–28; n = 17) and early third trimester (week 29–34; n = 17) in comparison with term CB (n = 18). The frequency 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 ± 14/105 mononuclear cells; p < 0.05) and correlated with the content of CD34+ progenitors (r = 0.73). Long-term culture initiating cells (LTC-IC) were enriched about 2.5-fold (6.7 ± 2.9 vs 2.6 ± 1.2/105 cells; p < 0.05). Progenitors from preterm CB could be expanded in stroma-free liquid cultures supplemented with hematopoietic growth factors as efficiently as progenitors from term neonates. In short-term cultures containing erythropoietin (Epo), interleukin (IL)-1, IL-3, and IL-6, or granulocyte- (G-) and granulocyte-macrophage colony-stimulating factor (GM-CSF) together with stem cell factor (SCF) or Flt3 ligand (FL), expansion of CFUs was six- to eightfold at week 1. In long-term cultures containing thrombopoietin (TPO) and FL, an approximately 1000-fold expansion of multilineage progenitors was observed at week 10. In summary, we show that preterm CB compared with term CB is richer in hematopoietic progenitors, and that precursors from preterm CB can be extensively expanded ex vivo. This may have implications for the development of transplantation and gene transfer strategies targeting circulating fetal stem cells.