Human umbilical cord blood cells differentiate into muscle in sjl muscular dystrophy mice
Human umbilical cord blood cells differentiate into muscle in sjl muscular dystrophy mice
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DOI：
10.1634/stemcells.22-6-981
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发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Brown, RH
中科院分区：
文献类型：
--
作者：
Kong, KY;Ren, JM;Brown, RH
肢带型肌营养不良2B型（LGMD-2B）和Miyoshi肌病（MM）都是由dysferlin（dysf）基因突变引起的。在这项研究中，我们使用dysferlin缺陷的sjl小鼠作为小鼠模型来研究LGMD-2B和MM的细胞治疗。一项单盲研究评估了人脐带血（HUCB）作为肌源性祖细胞来源的治疗潜力。干细胞。使用了三组供体细胞：未分级的单核HUCB细胞、经亚分级以富集谱系表面标志物阴性（LIN-）和实质上富集CD 34表面标志物（CD 34（+））的细胞的HUCB和经辐照的对照脾细胞。我们给每只动物静脉注射了1 × 10（6）个供体细胞，并在移植后的不同时间点（1-12周）对它们实施安乐死。从注射前一天至人道处死时，所有动物均接受免疫抑制（FK 506和来氟米特）。免疫组织化学分析证明，在移植后12周，来自整个HUCB和LIN（-）CD 34（+/-）富集的HUCB亚组的少量人细胞移植到受体肌肉中以表达dysferlin和人特异性肌营养不良蛋白。我们的结论是肌源性祖细胞存在于HUCB中，静脉注射后它们可以扩散到肌肉中，并且它们能够在宿主肌肉中肌源性分化。
Limb girdle muscular dystrophy type 2B form (LGMD-2B) and Miyoshi myopathy (MM) are both caused by mutations in the dysferlin (dysf) gene. In this study, we used dysferlin-deficient sjl mice as a mouse model to study cell therapy for LGMD-2B and MM. A single-blind study evaluated the therapeutic potential of human Umbilical cord blood (HUCB) as a source of myogenic progenitor stern cells. Three groups of donor cells were used: unfractionated mononuclear HUCB cells, HUCB subfractionated to enrich for cells that were negative for lineage surface markers (LIN-) and substantially enriched for the CD34 surface marker (CD34(+)), and irradiated control spleen cells. We administrated 1 x 10(6) donor cells to each animal intravenously and euthanized them at different time points (1-12 weeks) after transplantation. All animals were immunosuppressed (FK506 and leflunomide) from the day before the injection until the time of euthanasia. Immunohistochemical analyses documented that a small number of human cells from the whole HUCB and LIN(-)CD34(+/-)-enriched HUCB subgroups engraft in the recipient muscle to express both dysferlin and human-specific dystrophin at 12 weeks after transplantation. We conclude that myogenic progenitor cells are present in the HUCB, that they can disseminate into muscle after intravenous administration, and that they are capable of myogenic differentiation in host muscle.