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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    • "In their review article [91], Matsumoto and colleagues highlighted and discussed four examples of biodental engineering applications and advancements. Egusa and colleagues demonstrated that gingival fibroblasts (GFs), easily obtained from gingival tissues, can be readily reprogrammed into iPS cells without Myc transduction or a specific system for the selection of successfully reprogrammed cells, thus making them a promising source of cells for investigating the basis of cellular reprogramming and pluripotency for future clinical applications [92] [93] "
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    • "Human gingiva has a unique ability to heal. This potential for regeneration may be explained by the presence of sub-populations of stem cells recently isolated and expanded from this tissue (Fournier et al. 2010; Egusa et al. 2010; Tomar et al. 2010). Currently, human gingival fibroblasts (GFs) are successfully implicated for cell therapy of many organs including cornea, trachea, urethra, vocal cords and in the reconstruction of eyelids (Fournier et al. 2013). "
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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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