School of Dentistry, Colgate Australian Clinical Dental Research Centre, University of Adelaide, Adelaide, SA, Australia.
J Periodontal Res. 2011 Aug;46(4):438-47. doi: 10.1111/j.1600-0765.2011.01358.x. Epub 2011 Mar 29.
Human induced pluripotent stem (iPS) cells, which have similar properties to human embryonic stem (hES) cells, have been generated from neonatal and adult human dermal fibroblasts by reprogramming. iPS cells have high pluripotency and differentiation potential, and may be a potential autologous stem cell source for future regenerative therapy.
iPS cell lines from human gingival fibroblasts and, for the first time, from periodontal ligament fibroblasts, were generated by reprogramming using a retroviral transduction cocktail of OCT3/4, SOX2, KLF4 and c-MYC. iPS induction was investigated through expression of the embryonic stem cell markers SSEA4, OCT4, NANOG, GCTM-2, TG30 and TRA-1-60. Following in vitro differentiation, the expression of genes for differentiation markers for ectoderm (SOX1, PAX6), mesoderm [RUNX1, T(Brachyury)] and endoderm (GATA4, AFP) was assessed by real-time RT-PCR. The ability to form teratomas following implantation into mouse testes was assessed by histology.
Human gingival fibroblast- and periodontal ligament fibroblast-derived iPS cells showed similar characteristics to hES cells. Both sets of iPS cells displayed colony morphology comparable to that of hES cells and expressed the hES cell-associated cell-surface antigens, SSEA3, SSEA4, GCTM-2, TG30 (CD9) and Tra-1-60, and the hES cell marker genes, OCT4, NANOG and GDF3. These iPS cells showed differentiation potential to form embryoid bodies in vitro and expressed genes for endoderm, ectoderm and mesoderm. Teratoma formation following implantation into mouse testes was observed.
These results demonstrate that iPS cells can be successfully generated from adult human gingival and periodontal ligament fibroblasts.
通过重编程，人诱导多能干细胞（iPS 细胞）已从新生儿和成人真皮成纤维细胞中生成，其具有与人胚胎干细胞（hES 细胞）相似的特性。iPS 细胞具有高多能性和分化潜能，可能成为未来再生治疗的潜在自体干细胞来源。
通过使用 OCT3/4、SOX2、KLF4 和 c-MYC 的逆转录病毒转导混合物，首次从人牙龈成纤维细胞和牙周韧带成纤维细胞中生成 iPS 细胞系。通过表达胚胎干细胞标志物 SSEA4、OCT4、NANOG、GCTM-2、TG30 和 TRA-1-60 来研究 iPS 诱导。通过实时 RT-PCR 评估体外分化后外胚层（SOX1、PAX6）、中胚层 [RUNX1、T（Brachyury）] 和内胚层（GATA4、AFP）分化标志物基因的表达。通过组织学评估植入小鼠睾丸后形成畸胎瘤的能力。
人牙龈成纤维细胞和牙周韧带成纤维细胞来源的 iPS 细胞显示出与 hES 细胞相似的特征。两组 iPS 细胞均表现出与 hES 细胞相似的集落形态，并表达 hES 细胞相关的细胞表面抗原 SSEA3、SSEA4、GCTM-2、TG30（CD9）和 Tra-1-60，以及 hES 细胞标记基因 OCT4、NANOG 和 GDF3。这些 iPS 细胞具有在体外形成类胚体的分化潜力，并表达内胚层、外胚层和中胚层基因。观察到植入小鼠睾丸后形成畸胎瘤。
这些结果表明，可以从成人牙龈和牙周韧带成纤维细胞中成功生成 iPS 细胞。
