Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice
Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice
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DOI：
10.1172/jci33493
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发表时间：
2008-07-01
影响因子：
15.9
通讯作者：
Bischoff, Joyce
中科院分区：
文献类型：
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作者：
Khan, Zia A.;Boscolo, Elisa;Bischoff, Joyce
婴儿血管瘤是一种由紊乱的血管组成的良性内皮肿瘤。它表现出独特的生命周期，先是出生后快速生长，然后缓慢退化为纤维脂肪残留物。在这里，我们报道了从血管瘤组织中分离出多能干细胞，这些干细胞在免疫缺陷小鼠中引起血管瘤样病变。根据干细胞标记物 CD133 的表达分离细胞，并从单个细胞扩增为克隆群。 CD133选择的细胞在植入免疫缺陷小鼠体内7天后产生了人类血管。细胞修复实验表明，当移植到第二受体时，细胞可以再次形成血管。人类血管表达 GLUT-1 和 merosin，这是婴儿血管瘤的免疫诊断标记物。植入两个月后，血管数量减少，人体脂肪细胞变得明显。 GFP的慢病毒表达用于证实血管瘤来源的细胞在免疫缺陷小鼠中形成血管和脂肪细胞。因此，当移植到免疫缺陷小鼠体内时，血管瘤衍生的细胞重现了婴儿血管瘤的独特进化——血管形成，随后退化为脂肪组织。总之，这项研究确定干细胞是婴儿血管瘤的细胞起源，并首次描述了这种常见婴儿肿瘤的动物模型。
Infantile hemangioma is a benign endothelial tumor composed of disorganized blood vessels. It exhibits a unique life cycle of rapid postnatal growth followed by slow regression to a fibrofatty residuum. Here, we have reported the isolation of multipotential stem cells from hemangioma tissue that give rise to hemangioma-like lesions in immunodeficient mice. Cells were isolated based on expression of the stem cell marker CD133 and expanded from single cells as clonal populations. The CD133-selected cells generated human blood vessels 7 days after implantation in immunodeficient mice. Cell retrieval experiments showed the cells could again form vessels when transplanted into secondary recipients. The human vessels expressed GLUT-1 and merosin, immunodiagnostic markers for infantile hemangioma. Two months after implantation, the number of blood vessels diminished and human adipocytes became evident. Lentiviral expression of GFP was used to confirm that the hemangioma-derived cells formed the blood vessels and adipocytes in the immunodeficient mice. Thus, when transplanted into immunodeficient mice, hemangioma-derived cells recapitulated the unique evolution of infantile hemangioma - the formation of blood vessels followed by involution to fatty tissue. In summary, this study identifies a stem cell as the cellular origin of infantile hemangioma and describes for what we believe is the first time an animal model for this common tumor of infancy.