iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin.
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.
Yan
Xing
X
Section of Oral and Diagnostic Sciences, Division of Endodontics, College of Dental Medicine, Columbia University, New York, New York, USA.
Qin
Haiyan
H
Qu
Cunye
C
Tuan
Rocky S
RS
Shi
Songtao
S
Huang
George T-J
GT
D000954:Antigens, Surface / Q000378:metabolism; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D003771:Dental Papilla / Q000166:cytology / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism; D014094:Tooth, Deciduous / Q000166:cytology / Q000378:metabolism; D014161:Transduction, Genetic
D000954:Antigens, Surface; D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C000715187:Lin28A protein, human; C489427:MYC protein, human; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011509:Proteoglycans; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D055746:Stage-Specific Embryonic Antigens; C107064:TRA-1-60 antigen, human; C066584:stage-specific embryonic antigen-4