iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin

Stem Cells Dev. 2010 Apr;19(4):469-80. doi: 10.1089/scd.2009.0314.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigens, Surface / metabolism
  • Cells, Cultured
  • Cellular Reprogramming*
  • Dental Papilla* / cytology
  • Dental Papilla* / metabolism
  • Dental Pulp* / cytology
  • Dental Pulp* / metabolism
  • Homeodomain Proteins / genetics
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Proteoglycans / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA-Binding Proteins / genetics
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Stage-Specific Embryonic Antigens / metabolism
  • Tooth, Deciduous* / cytology
  • Tooth, Deciduous* / metabolism
  • Transduction, Genetic*

Substances

  • Antigens, Surface
  • GKLF protein
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • Lin28A protein, human
  • MYC protein, human
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proteoglycans
  • Proto-Oncogene Proteins c-myc
  • RNA-Binding Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Stage-Specific Embryonic Antigens
  • TRA-1-60 antigen, human
  • stage-specific embryonic antigen-4