Lack of self-renewal capacity in Fancc-/-Stem cells after ex vivo expansion
Lack of self-renewal capacity in Fancc-/-Stem cells after ex vivo expansion
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DOI：
10.1634/stemcells.2004-0356
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发表时间：
2005-09-01
期刊：
影响因子：
5.2
通讯作者：
Carreau, M
中科院分区：
文献类型：
--
作者：
Habi, O;Delisle, MC;Carreau, M
范可尼贫血（FA）血液学表现的治疗首先通过尝试用雄激素或造血生长因子刺激造血来支持。然而，FA患者血液学表现的长期治疗方法是骨髓（BM）或脐带血干细胞移植。对于 HLA 匹配的兄弟姐妹捐献者来说，骨髓移植的成功率相当高，但不幸的是，对于 HLA 匹配的非亲属捐献者来说，骨髓移植的成功率很低。对于那些没有兄弟姐妹捐赠者的患者来说，另一种治疗方法可能是将基因转移到造血干细胞中。由于 FA 患者的干细胞/祖细胞数量减少，造血干细胞的离体扩增将是基因转移方案中的关键步骤。使用FA小鼠模型Fancc(-/-)，我们测试了CD34(-)造血干细胞支持离体扩增的能力。我们确定Fancc(-/-) CD34(-)干细胞在培养后重建能力降低，自我更新能力明显降低，如二次移植所示。这些结果表明 FA 干细胞可能不太适合在基因转移或移植方案之前进行离体扩增。
Treatments of the hematological manifestation in Fanconi anemia (FA) are first supported by attempts to stimulate hematopoiesis with androgens or hematopoietic growth factors. However, the long-term curative treatment of the hematological manifestation in FA patients is bone marrow (BM) or cord blood stem cell transplantation. The success rate for BM transplantation is fairly high with HLA-matched sibling donors but is, unfortunately, low with HLA-matched unrelated donors. An alternative curative treatment for those patients with no sibling donors might be gene transfer into hematopoietic stem cells. Because FA patients have reduced numbers of stem/progenitor cells, ex vivo expansion of hematopoietic stem cells would be a crucial step in gene transfer protocols. Using the FA mouse model, Fancc(-/-), we tested the ability of CD34(-) hematopoietic stem cells to support ex vivo expansion. We determined that Fancc(-/-) CD34(-) stem cells have reduced reconstitution ability and markedly reduced self-renewal ability after culture, as shown by secondary transplants. These results indicate that FA stem cells may not be well suited for ex vivo expansion before gene transfer or transplantation protocols.