A New Immuno-, Dystrophin- Deficient Model, the NSG-mdx4Cv Mouse, Provides Evidence for Functional Improvement Following Allogeneic Satellite Cell Transplantation
A New Immuno-, Dystrophin- Deficient Model, the NSG-mdx4Cv Mouse, Provides Evidence for Functional Improvement Following Allogeneic Satellite Cell Transplantation
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DOI：
10.1002/stem.1402
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发表时间：
2013-08-01
期刊：
影响因子：
5.2
通讯作者：
Kyba, Michael
中科院分区：
文献类型：
--
作者：
Arpke, Robert W.;Darabi, Radbod;Kyba, Michael
将肌源性细胞群体移植到免疫缺陷受体是评估该细胞群体体内肌肉生成能力的一种极好的方法。为了促进同种和异种肌肉形成细胞在小鼠体内的移植，我们开发了一种新的免疫缺陷性肌营养不良症模型，NSG-MDX(4CV)小鼠。IL2RG突变与X染色体上的DMD基因相关联，同时耗尽NK细胞并抑制胸腺淋巴瘤，这一问题限制了SCID/MDX模型的实用。NSG-MDX(4CV)小鼠表现出与传统MDX小鼠相似的肌肉营养不良。我们发现，这种动物支持猪和狗肌肉单个核细胞的强健植入。通过流式细胞仪预期分离的卫星细胞是否可以在移植后带来功能上的好处，这一问题一直存在争议。使用同种异体Pax7-ZsGreen供体和NSG-MDX(4CV)受体，我们明确地证明，与假注射对照组相比，仅有900个FACS分离的卫星细胞可以在体内提供功能性再生，表现为细胞移植肌肉的平均最大力量生成能力增加。这些研究突出了卫星细胞改善肌肉功能的潜力，以及NSG-MDX(4CV)模型在肌肉再生和Duchenne肌营养不良治疗研究中的应用。干细胞2013；31：1611-1620
Transplantation of a myogenic cell population into an immunodeficient recipient is an excellent way of assessing the in vivo muscle-generating capacity of that cell population. To facilitate both allogeneic and xenogeneic transplantations of muscle-forming cells in mice, we have developed a novel immunodeficient muscular dystrophy model, the NSG-mdx(4Cv) mouse. The IL2Rg mutation, which is linked to the Dmd gene on the X chromosome, simultaneously depletes NK cells and suppresses thymic lymphomas, issues that limit the utility of the SCID/mdx model. The NSG-mdx(4Cv) mouse presents a muscular dystrophy of similar severity to the conventional mdx mouse. We show that this animal supports robust engraftment of both pig and dog muscle mononuclear cells. The question of whether satellite cells prospectively isolated by flow cytometry can confer a functional benefit upon transplantation has been controversial. Using allogeneic Pax7-ZsGreen donors and NSG-mdx(4Cv) recipients, we demonstrate definitively that as few as 900 FACS-isolated satellite cells can provide functional regeneration in vivo, in the form of an increased mean maximal force-generation capacity in cell-transplanted muscles, compared to a sham-injected control group. These studies highlight the potency of satellite cells to improve muscle function and the utility of the NSG-mdx(4Cv) model for studies on muscle regeneration and Duchenne muscular dystrophy therapy. STEM Cells2013;31:1611-1620