title: Generation of Neural Crest-Like Cells From Human Periodontal Ligament Cell-Derived Induced Pluripotent Stem Cells.
abstract: Neural crest cells (NCC) hold great promise for tissue engineering, however the inability to easily obtain large numbers of NCC is a major factor limiting their use in studies of regenerative medicine. Induced pluripotent stem cells (iPSC) are emerging as a novel candidate that could provide an unlimited source of NCC. In the present study, we examined the potential of neural crest tissue-derived periodontal ligament (PDL) iPSC to differentiate into neural crest-like cells (NCLC) relative to iPSC generated from a non-neural crest derived tissue, foreskin fibroblasts (FF). We detected high HNK1 expression during the differentiation of PDL and FF iPSC into NCLC as a marker for enriching for a population of cells with NCC characteristics. We isolated PDL iPSC- and FF iPSC-derived NCLC, which highly expressed HNK1. A high proportion of the HNK1-positive cell populations generated, expressed the MSC markers, whilst very few cells expressed the pluripotency markers or the hematopoietic markers. The PDL and FF HNK1-positive populations gave rise to smooth muscle, neural, glial, osteoblastic and adipocytic like cells and exhibited higher expression of smooth muscle, neural, and glial cell-associated markers than the PDL and FF HNK1-negative populations. Interestingly, the HNK1-positive cells derived from the PDL-iPSC exhibited a greater ability to differentiate into smooth muscle, neural, glial cells and adipocytes, than the HNK1-positive cells derived from the FF-iPSC. Our work suggests that HNK1-enriched NCLC from neural crest tissue-derived iPSC more closely resemble the phenotypic and functional hallmarks of NCC compared to the HNK1-low population and non-neural crest iPSC-derived NCLC. J. Cell. Physiol. 232: 402-416, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, Adelaide, Australia. tomokiyo@dent.kyushu-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tomokiyo
authors.affiliation: Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, Adelaide, Australia.|South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Hynes
authors.affiliation: Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, Adelaide, Australia.|South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
authors.forename: Jia
authors.initials: J
authors.lastname: Ng
authors.affiliation: Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, Adelaide, Australia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Menicanin
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, SA, Australia.|Mesenchymal Stem Cell Laboratory, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Esther
authors.initials: E
authors.lastname: Camp
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, SA, Australia.|Mesenchymal Stem Cell Laboratory, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia.|SA Pathology, Adelaide, SA, Australia.
authors.forename: Agnes
authors.initials: A
authors.lastname: Arthur
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, SA, Australia.|Mesenchymal Stem Cell Laboratory, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
authors.affiliation: Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, Adelaide, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Mark Bartold
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D048430:Cell Shape; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D009432:Neural Crest / Q000166:cytology*; D010513:Periodontal Ligament / Q000166:cytology*
chemical_list: D015415:Biomarkers