Section of Oral and Diagnostic Sciences, Division of Endodontics, College of Dental Medicine, Columbia University, New York, New York, USA.
Stem Cells Dev. 2010 Apr;19(4):469-80. doi: 10.1089/scd.2009.0314.
Generation of induced pluripotent stem (iPS) cells holds a great promise for regenerative medicine and other aspects of clinical applications. Many types of cells have been successfully reprogrammed into iPS cells in the mouse system; however, reprogramming human cells have been more difficult. To date, human dermal fibroblasts are the most accessible and feasible cell source for iPS generation. Dental tissues derived from ectomesenchyme harbor mesenchymal-like stem/progenitor cells and some of the tissues have been treated as biomedical wastes, for example, exfoliated primary teeth and extracted third molars. We asked whether stem/progenitor cells from discarded dental tissues can be reprogrammed into iPS cells. The 4 factors Lin28/Nanog/Oct4/Sox2 or c-Myc/Klf4/Oct4/Sox2 carried by viral vectors were used to reprogram 3 different dental stem/progenitor cells: stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), and dental pulp stem cells (DPSCs). We showed that all 3 can be reprogrammed into iPS cells and appeared to be at a higher rate than fibroblasts. They exhibited a morphology indistinguishable from human embryonic stem (hES) cells in cultures and expressed hES cell markers SSEA-4, TRA-1-60, TRA-1-80, TRA-2-49, Nanog, Oct4, and Sox2. They formed embryoid bodies in vitro and teratomas in vivo containing tissues of all 3 germ layers. We conclude that cells of ectomesenchymal origin serve as an excellent alternative source for generating iPS cells.
诱导多能干细胞（iPS）的产生为再生医学和临床应用的其他方面带来了巨大的希望。在小鼠系统中，许多类型的细胞已成功被重编程为 iPS 细胞；然而，重编程人类细胞更加困难。迄今为止，人类真皮成纤维细胞是 iPS 生成最容易获得和最可行的细胞来源。外胚间充质来源的牙组织中含有间充质样干细胞/祖细胞，其中一些组织已被视为生物医学废物，例如，脱落的乳牙和拔出的第三磨牙。我们想知道丢弃的牙组织中的干细胞/祖细胞是否可以被重编程为 iPS 细胞。我们使用携带 Lin28/Nanog/Oct4/Sox2 或 c-Myc/Klf4/Oct4/Sox2 的病毒载体来重编程 3 种不同的牙干细胞/祖细胞：脱落乳牙干细胞（SHED）、根尖乳头干细胞（SCAP）和牙髓干细胞（DPSCs）。我们表明，所有这 3 种细胞都可以被重编程为 iPS 细胞，而且似乎比成纤维细胞的效率更高。它们在培养物中呈现出与人类胚胎干细胞（hES）细胞无法区分的形态，并表达 hES 细胞标志物 SSEA-4、TRA-1-60、TRA-1-80、TRA-2-49、Nanog、Oct4 和 Sox2。它们在体外形成胚状体，并在体内形成含有 3 个胚层组织的畸胎瘤。我们的结论是，外胚间充质来源的细胞是生成 iPS 细胞的极好替代来源。
