Wyrsch A, dalle Carbonare V, Jansen W, Chklovskaia E, Nissen C, Surbek D, Holzgreve W, Tichelli A, Wodnar-Filipowicz A
Department of Research, University Hospital Basel, Switzerland.
Exp Hematol. 1999 Aug;27(8):1338-45. doi: 10.1016/s0301-472x(99)00059-4.
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/ 10(5) 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 +/- 1.2/10(5) 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.
人脐带血（CB）已被公认为是用于移植的造血干细胞来源。虽然足月妊娠新生儿CB的造血特性已得到充分表征，但对于孕早期CB的了解却很少。我们分析了孕中期（第16 - 28周；n = 17）和孕晚期早期（第29 - 34周；n = 17）早产CB中原始和定向造血祖细胞的含量及生长特性，并与足月CB（n = 18）进行比较。早产CB中CD34 +和CD34 + CD38 -细胞的频率显著高于足月CB（平均值分别为2.51%和0.56%，而足月CB为0.88%和0.13%；p < 0.002）。早产CB中集落形成单位（CFU）的数量约高出两倍（230 ± 6对133 ± 14/10⁵个单核细胞；p < 0.05），且与CD34 +祖细胞的含量相关（r = 0.73）。长期培养起始细胞（LTC - IC）富集约2.5倍（6.7 ± 2.9对2.6 ± 1.2/10⁵个细胞；p < 0.05）。早产CB中的祖细胞在添加造血生长因子的无基质液体培养中能够与足月新生儿的祖细胞一样高效地扩增。在含有促红细胞生成素（Epo）、白细胞介素（IL）-1、IL - 3和IL - 6，或粒细胞（G）-和粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）以及干细胞因子（SCF）或Flt3配体（FL）的短期培养中，CFU在第1周时扩增了6至8倍。在含有血小板生成素（TPO）和FL的长期培养中，在第10周时观察到多谱系祖细胞扩增了约1000倍。总之，我们表明与足月CB相比，早产CB富含造血祖细胞，并且早产CB的前体细胞能够在体外广泛扩增。这可能对针对循环胎儿干细胞的移植和基因转移策略的发展具有重要意义。
