Differentiation of Induced Pluripotent Stem Cells Into Dental Mesenchymal Cells

Differentiation of Induced Pluripotent Stem Cells Into Dental Mesenchymal Cells
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DOI:
10.1089/scd.2011.0210
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发表时间:
2012-05-01
影响因子:
4
通讯作者:
Harada, Hidemitsu
Harada, Hidemitsu
中科院分区:
医学3区
文献类型:
--
作者:
Otsu, Keishi;Kishigami, Ryota;Harada, Hidemitsu

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与胚胎干细胞类似,诱导多能干细胞(iPS)在适当的诱导下可以分化为各种细胞类型,因此可能是再生医学的宝贵细胞来源。然而,尚未报道iPS细胞分化为牙源性细胞用于牙齿再生。在这里,我们证明了源自小鼠iPS细胞的神经嵴样细胞(NCLC)具有分化为牙源性间充质细胞的潜力。我们开发了一种有效的培养方案来诱导小鼠iPS细胞分化为NCLC。我们证实,细胞表现出神经嵴(NC)细胞标志物证明免疫细胞化学,流式细胞术,实时逆转录聚合酶链反应。此外,在NCLC和小鼠牙齿上皮的重组培养物中,NCLC表现出涉及牙齿间充质细胞的基因表达模式。部分NCLC也表达牙本质涎蛋白。小鼠牙上皮条件培养液进一步促进NCLC向成牙本质细胞分化。这些结果表明,iPS细胞是牙齿再生和牙齿发育研究的有用细胞来源。
Similar to embryonic stem cells, induced pluripotent stem (iPS) cells can differentiate into various cell types upon appropriate induction, and thus, may be valuable cell sources for regenerative medicine. However, iPS cells have not been reported to differentiate into odontogenic cells for tooth regeneration. Here we demonstrated that neural crest-like cells (NCLC) derived from mouse iPS cells have the potential to differentiate into odontogenic mesenchymal cells. We developed an efficient culture protocol to induce the differentiation of mouse iPS cells into NCLC. We confirmed that the cells exhibited neural crest (NC) cell markers as evidenced by immunocytochemistry, flow cytometry, and real-time reverse transcription-polymerase chain reaction. Further, in recombination cultures of NCLC and mouse dental epithelium, NCLC exhibited a gene expression pattern involving dental mesenchymal cells. Some NCLC also expressed dentin sialoprotein. Conditioned medium of mouse dental epithelium cultures further enhanced the differentiation of NCLC into odontoblasts. These results suggest that iPS cells are useful cell sources for tooth regeneration and tooth development studies.