Unique multipotent cells in adult human mesenchymal cell populations
Unique multipotent cells in adult human mesenchymal cell populations
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DOI：
10.1073/pnas.0911647107
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发表时间：
2010-05-11
影响因子：
11.1
通讯作者：
Dezawa, Mari
中科院分区：
文献类型：
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作者：
Kuroda, Yasumasa;Kitada, Masaaki;Dezawa, Mari
我们发现成人干细胞可以从单个细胞中产生具有三种胚层特征的细胞。这些细胞具有抗应力性，可以从培养的皮肤成纤维细胞或骨髓基质细胞中分离出来，也可以直接从骨髓抽吸物中分离出来。这些细胞可以自我更新；在悬浮培养中形成特征性细胞簇，表达一组与多能性相关的基因；在体外和体内均可分化为内胚层、外胚层和中胚层细胞。当通过局部或静脉注射将这些细胞移植到免疫缺陷小鼠体内时，这些细胞会整合到受损的皮肤、肌肉或肝脏中，并在各自的组织中分化为细胞角蛋白14阳性、肌营养不良蛋白阳性或白蛋白阳性细胞。此外，它们可以高效地分离为SSEA-3（+）细胞。与真正的胚胎干细胞不同，它们的增殖活性不是很高，在免疫缺陷小鼠睾丸中不会形成畸胎瘤。因此，不需要引入外源基因，就可以通过容易获得的成人间充质细胞获得能够产生三种胚层多种细胞类型的非致瘤性干细胞。这些独特的细胞将有利于细胞治疗和生物医学研究。
We found adult human stem cells that can generate, from a single cell, cells with the characteristics of the three germ layers. The cells are stress-tolerant and can be isolated from cultured skin fibroblasts or bone marrow stromal cells, or directly from bone marrow aspirates. These cells can self-renew; form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency; and can differentiate into endodermal, ectodermal, and mesodermal cells both in vitro and in vivo. When transplanted into immunodeficient mice by local or i.v. injection, the cells integrated into damaged skin, muscle, or liver and differentiated into cytokeratin 14-, dystrophin-, or albumin-positive cells in the respective tissues. Furthermore, they can be efficiently isolated as SSEA-3(+) cells. Unlike authentic ES cells, their proliferation activity is not very high and they do not form teratomas in immunodeficient mouse testes. Thus, nontumorigenic stem cells with the ability to generate the multiple cell types of the three germ layers can be obtained through easily accessible adult human mesenchymal cells without introducing exogenous genes. These unique cells will be beneficial for cell-based therapy and biomedical research.