iPS Cells Reprogrammed From Human Mesenchymal-Like Stem/Progenitor Cells of Dental Tissue Origin

Abstract

Generation of induced pluripotent stem (iPS) cells holds a great promise for regenerative medicine and other aspects of clinical applications. Many types of cells have been successfully reprogrammed into iPS cells in the mouse system; however, reprogramming human cells have been more difficult. To date, human dermal fibroblasts are the most accessible and feasible cell source for iPS generation. Dental tissues derived from ectomesenchyme harbor mesenchymal-like stem/progenitor cells and some of the tissues have been treated as biomedical wastes, for example, exfoliated primary teeth and extracted third molars. We asked whether stem/progenitor cells from discarded dental tissues can be reprogrammed into iPS cells. The 4 factors Lin28/Nanog/Oct4/Sox2 or c-Myc/Klf4/Oct4/Sox2 carried by viral vectors were used to reprogram 3 different dental stem/progenitor cells: stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), and dental pulp stem cells (DPSCs). We showed that all 3 can be reprogrammed into iPS cells and appeared to be at a higher rate than fibroblasts. They exhibited a morphology indistinguishable from human embryonic stem (hES) cells in cultures and expressed hES cell markers SSEA-4, TRA-1-60, TRA-1-80, TRA-2-49, Nanog, Oct4, and Sox2. They formed embryoid bodies in vitro and teratomas in vivo containing tissues of all 3 germ layers. We conclude that cells of ectomesenchymal origin serve as an excellent alternative source for generating iPS cells.

Notch/Wnt cross-signalling regulates stemness of dental pulp stem cells through expression of neural crest and core pluripotency factors

“…Canonical Notch and Wnt signalling pathways are described as pivotal regulators of stemness and pluripotency Dravid et al, 2005;Fox et al, 2008;Li and Chen, 2012;Lluis et al, 2008;Lowell et al, 2006;Park et al, 2008;Simandi et al, 2016;Yan et al, 2010) and their pharmacological manipulation has already been tested as a strategy to enhance either cell differentiation (Kitajima et al, 2016) or cell reprogramming (Ichida et al, 2014). Notch inhibition by γ-secretase blockers is associated with an increased efficiency of keratinocyte reprogramming (Ichida et al, 2014).…”

<b>Induction of neural crest cells from human dental pulp-derived induced pluripotent stem </b><b>cells </b>

“…Therefore, NCCs could represent a key cell source for tooth-tissue engineering. Induced pluripotent stem (iPS) cells are generated from a variety of somatic cells such as dermal fibroblasts (53,54), blood cells, (12) and dental pulp cells (42,55,59,62) by induction with several factors. iPS cells are able to differentiate into all three germ layers with large-scale expansion (12, 42, 53-55, 59, 62), bypassing the potential ethical problems of using embryonic stem (ES) cells.…”

Stem Cells: Tools for Dental Tissues Regeneration

“…However, reprogramming human cells seems to be more difficult. Stem/progenitor cells from discarded dental tissues can be reprogrammed into iPS cells [43]. Human dermal fibroblasts were the first type of cells being reprogrammed into iPS cells.…”