Busulfan administration flexibility increases the applicability of scid repopulating cell assay in NSG mouse model.
Busulfan administration flexibility increases the applicability of scid repopulating cell assay in NSG mouse model.
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DOI：
10.1371/journal.pone.0074361
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Brunet de la Grange P
中科院分区：
文献类型：
--
作者：
Chevaleyre J;Duchez P;Rodriguez L;Vlaski M;Villacreces A;Conrad-Lapostolle V;Praloran V;Ivanovic Z;Brunet de la Grange P
尽管在表型特征方面最近取得了进展，但能够在免疫缺陷小鼠中识别和量化人类造血干细胞（HSC）的异种移植模型仍然是恰当研究人类HSC功能的唯一方法。然而，这些体内实验在技术上要求高、耗时且昂贵。实际上，HSC在小鼠体内的植入需要通过照射或细胞毒性药物对动物进行预处理，以使注入的细胞归巢到特定的干细胞微环境中，并随后在骨髓中扩增和分化。最近，白消安对动物进行预处理的方法的发展相较于照射提高了实验的灵活性。
为了进一步促进这些复杂实验的组织，我们研究了延长小鼠预处理和细胞注射之间的时间间隔对植入效率的影响。同时，我们还探讨了白消安剂量、小鼠性别以及静脉注射途径（尾静脉或眼眶后静脉）对植入效率的作用。
我们表明，在NSG模型中，长达7天的时间间隔不会改变人类HSC的植入效率。此外，对用2×25mg/kg白消安预处理的雌性小鼠进行眼眶后静脉细胞注射似乎是在异种移植实验中检测人类HSC的最合适方案。
Xenotransplantation models allowing the identification and quantification of human Hematopoietic stem cells (HSC) in immunodeficient mice remain the only way to appropriately address human HSC function despite the recent progress in phenotypic characterization. However, these in vivo experiments are technically demanding, time consuming and expensive. Indeed, HSCs engraftment in mouse requires pre-conditioning of animals either by irradiation or cytotoxic drugs to allow homing of injected cells in specific stem cell niches and their subsequent expansion and differentiation in bone marrow. Recently, the development of busulfan pre-conditioning of animals improved the flexibility of experimentation in comparison with irradiation. In order to further facilitate the organization of these complex experiments we investigated the effect of extending the period between mice pre-conditioning and cell injection on the engraftment efficiency. In the meantime, we also explored the role of busulfan doses, mouse gender and intravenous injection route (caudal or retro orbital) on engraftment efficiency. We showed that a period of up to 7 days did not modify engraftment efficiency of human HSCs in NSG model. Moreover, retro orbital cell injection to female mice pre-conditioned with 2x25 mg/kg of busulfan seems to be the best adapted schema to detect the human HSC in xenotransplantation experiments.
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影响因子：
64.8
作者：
Quintana, Elsa;Shackleton, Mark;Sabel, Michael S.;Fullen, Douglas R.;Johnson, Timothy M.;Morrison, Sean J.
通讯作者：
Morrison, Sean J.
影响因子：
20.3
作者：
Notta, Faiyaz;Doulatov, Sergei;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
20.3
作者：
McDermott, Sean P.;Eppert, Kolja;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
4.4
作者：
Shultz, LD;Lyons, BL;Handgretinger, R
通讯作者：
Handgretinger, R
影响因子：
5.2
作者：
Ivanovic, Z;Hermitte, F;Praloran, V
通讯作者：
Praloran, V