Gingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells

University of Colorado, Boulder, United States of America
PLoS ONE (Impact Factor: 3.23). 09/2010; 5(9):e12743. DOI: 10.1371/journal.pone.0012743
Source: PubMed


Induced pluripotent stem (iPS) cells efficiently generated from accessible tissues have the potential for clinical applications. Oral gingiva, which is often resected during general dental treatments and treated as biomedical waste, is an easily obtainable tissue, and cells can be isolated from patients with minimal discomfort.
We herein demonstrate iPS cell generation from adult wild-type mouse gingival fibroblasts (GFs) via introduction of four factors (Oct3/4, Sox2, Klf4 and c-Myc; GF-iPS-4F cells) or three factors (the same as GF-iPS-4F cells, but without the c-Myc oncogene; GF-iPS-3F cells) without drug selection. iPS cells were also generated from primary human gingival fibroblasts via four-factor transduction. These cells exhibited the morphology and growth properties of embryonic stem (ES) cells and expressed ES cell marker genes, with a decreased CpG methylation ratio in promoter regions of Nanog and Oct3/4. Additionally, teratoma formation assays showed ES cell-like derivation of cells and tissues representative of all three germ layers. In comparison to mouse GF-iPS-4F cells, GF-iPS-3F cells showed consistently more ES cell-like characteristics in terms of DNA methylation status and gene expression, although the reprogramming process was substantially delayed and the overall efficiency was also reduced. When transplanted into blastocysts, GF-iPS-3F cells gave rise to chimeras and contributed to the development of the germline. Notably, the four-factor reprogramming efficiency of mouse GFs was more than 7-fold higher than that of fibroblasts from tail-tips, possibly because of their high proliferative capacity.
These results suggest that GFs from the easily obtainable gingival tissues can be readily reprogrammed into iPS cells, thus making them a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications. In addition, high-quality iPS cells were generated from mouse GFs without Myc transduction or a specific system for reprogrammed cell selection.

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Available from: Hiroshi Egusa, Jul 05, 2014
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    • "); gingival tissue (Egusa et al. 2010; Wada et al. 2011); and PDL stem cells (Wada et al. 2011). A comparison performed by Yan et al. (2010) identified that the reprogramming efficiency appeared to be greater from dental-derived tissues than human fibroblast cells. "
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    • "Very recently, the in vivo efficacy of utilizing GMSCs in bone regeneration was demonstrated in a mandibular defect as well as a critical-sized calvarial defect model in rats [53]. Furthermore, these cells gave rise to high-quality iPS cells, which suggests that gingival tissue is also a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications [54]. "
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