Department of Molecular Biology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
J Biosci Bioeng. 2010 Sep;110(3):345-50. doi: 10.1016/j.jbiosc.2010.03.004. Epub 2010 Apr 8.
Induced pluripotent stem (iPS) cells are one of the most promising sources for cell therapy in regenerative medicine. Using a patient's own genetically identical and histocompatible cells is the ideal way to practice personalized regenerative medicine. For personalized iPS cell therapy, the prerequisites for cell source preparation are a simple and safe procedure, no aesthetic or functional damage, and quick wound healing. Oral mucosa fibroblasts (OFs) may have high potential to fulfill these requirements. In this study, biopsy was performed in a dental chair; no significant incisional damage was recognized and rapid wound healing (within a week) was observed. We generated human iPS cells from the isolated OFs via the retroviral gene transfer of OCT4, SOX2, c-MYC, and KLF4. Reprogrammed cells showed ES-like morphology and expressed undifferentiated markers such as OCT4, NANOG, SSEA4, TRA-1-60, and TRA-1-81. Subsequent in vitro and in vivo analyses confirmed the pluripotency of resultant iPS cells, which matched the criteria for iPS cells. In addition, we found that the endogenous expression levels of c-MYC and KLF4 in OFs were similar to those in dermal fibroblasts. Taken together, we propose that OFs could be a practical source for preparing iPS cells to achieve personalized regenerative medicine in the near future.
诱导多能干细胞（iPS 细胞）是再生医学中细胞治疗最有前途的来源之一。使用患者自身遗传上相同且组织相容性的细胞是实践个性化再生医学的理想方法。对于个性化 iPS 细胞治疗，细胞来源准备的前提条件是简单、安全的程序，无美观或功能损伤，且伤口愈合迅速。口腔黏膜成纤维细胞（OFs）可能具有满足这些要求的高潜力。在这项研究中，我们在牙科椅上进行了活检；未观察到明显的切口损伤，且伤口愈合迅速（一周内）。我们通过 OCT4、SOX2、c-MYC 和 KLF4 的逆转录病毒基因转移，从分离的 OFs 中生成了人类 iPS 细胞。重编程细胞表现出 ES 样形态，并表达未分化标志物，如 OCT4、NANOG、SSEA4、TRA-1-60 和 TRA-1-81。随后的体外和体内分析证实了所得 iPS 细胞的多能性，符合 iPS 细胞的标准。此外，我们发现 OFs 中 c-MYC 和 KLF4 的内源性表达水平与真皮成纤维细胞相似。综上所述，我们提出 OFs 可能是制备 iPS 细胞以实现个性化再生医学的实用来源。
