Simultaneous maintenance of human cord blood SCID-repopulating cells and expansion of committed progenitors at low O2 concentration (3%)

Simultaneous maintenance of human cord blood SCID-repopulating cells and expansion of committed progenitors at low O2 concentration (3%)
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DOI:
10.1634/stemcells.22-5-716
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发表时间:
2004-01-01
期刊:
影响因子:
5.2
通讯作者:
Praloran, V
Praloran, V
中科院分区:
医学2区
文献类型:
--
作者:
Ivanovic, Z;Hermitte, F;Praloran, V

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在本研究中,我们验证了这样一个假设:在适当低氧浓度下对脐带血CD34(+)细胞进行液体培养(LCs),能够同时实现集落形成细胞(CFC)的扩增以及非肥胖型糖尿病/重症联合免疫缺陷小鼠造血重建细胞(SRC)的维持。我们首先发现3%是最低氧浓度,在此浓度下CFC的扩增速率与20%氧浓度时相同。在此我们报道,在3%氧浓度下对脐带血CD34(+)细胞进行7天的液体培养,其对SRC的维持效果优于20%氧浓度,并且能在不改变CD34(+)细胞增殖的情况下实现类似的CFC扩增(35 - 50倍)。它们的表型特征(抗原:HLA - DR、CD117、CD33、CD13、CD11b、CD14、CD15和CD38)未发生改变,但CD133除外,其在3%氧浓度下表达较低。这些结果表明,与骨髓中相似的低氧浓度通过促进干细胞的更新分裂参与了造血的调控。这种避免干细胞耗竭的扩增方法在造血移植中可能具有极其重要的意义,因为它允许在成人中使用小体积的移植物。
In the present work, we tested the hypothesis that liquid cultures (LCs) of cord blood CD34(+) cells at an appropriate low O-2 concentration could simultaneously allow colony-forming cell (CFC) expansion and nonobese diabetic/severe combined immunodeficiency mice-repopulating cell (SRC) maintenance. We first found that 3% was the minimal O-2 concentration, still allowing the same rate of CFC expansion as at 20% O-2. We report here that 7-day LCs of cord blood CD34(+) cells at 3% O-2 maintain SRC better than at 20% O-2 and allow a similar amplification of CFCs (35- to 50-fold) without modifying the CD34(+) cell proliferation. Their phenotypic profile (antigens: HLA-DR, CD117, CD33, CD13, CD11b, CD14, CD15, and CD38) was not modified, with exception of CD133, whose expression was lower at 3% O-2. These results suggest that low O-2 concentrations similar to those found in bone marrow participates in the regulation of hematopoiesis by favoring stem cell-renewing divisions. This expansion method that avoids stem cell exhaustion could be of paramount interest in hematopoietic transplantation by allowing the use of small-size grafts in adults.